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Intelligent Design, the best explanation of Origins

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Intelligent Design, the best explanation of Origins » Origin of life » Translation through ribosomes, amazing nano machines

Translation through ribosomes, amazing nano machines

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26Translation through ribosomes,  amazing nano machines - Page 2 Empty A reply to Dimiter Kunnev on Mon Sep 28, 2020 3:35 pm

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A reply to Dimiter Kunnev

https://reasonandscience.catsboard.com/t1661p25-translation-through-ribosomes-amazing-nano-machines#8008

In reply to my email

How ribosomes are like Russian dolls
https://reasonandscience.catsboard.com/t1661-translation-through-ribosomes-amazing-nano-machines#8006

Dimiter Kunnev did send me following reply:
Hi guys, please note that in order for Ribosome to function as protein synthesis needs only PTC even in a primitive form and something to hold it. I'm sending several papers to consider. The entire concept for the irreducibly complex ribosome is only wishful thinking. Enjoy

It is nice first to read the papers and then give answers. From your answer, it is clear that you don't know what you are talking about. Here is the evidence that in order to have peptide synthesis you need only short RNA. Also, I'm sending the 2012 and 2016 Anolles papers where is presented IN DETAILS loop by loop, helix by helix entire evolution of the ribosome. You can see that the ribosomal RNA and tRNA are coevolved EXACTLY as suppose to be according to step by step evolutionary development. ALL DATA CLEARLY SUGGESTS THAT THE RIBOSOME IS NOT IRREDUCEBLY COMPLEX. Your hypothesis for SUDDEN ID dependent formation is NOT supported at all. Please do not answer unprepared and after all, please acknowledge the data even that contradicts your view.

Following science papers were annexed in the first reply:
Ribosomal proteins as documents of the transition from unstructured (poly)peptides to folded proteins
https://www.sciencedirect.com/science/article/pii/S1047847717300606
Peptidyl-transferase ribozymes: trans reactions, structural characterization and ribosomal RNA-like features
https://www.sciencedirect.com/science/article/pii/S1047847717300606
Could a Proto-Ribosome Emerge Spontaneously in the Prebiotic World?
https://europepmc.org/article/med/27941673
History of the ribosome and the origin of translation
https://www.pnas.org/content/112/50/15396

Here my reply & comments:

Claim: in order for Ribosome to function as protein synthesis needs only PTC even in a primitive form 
Reply: The Ancient History of Peptidyl Transferase Center Formation as Told by Conservation and Information Analyses
https://www.mdpi.com/2075-1729/10/8/134
The PTC region has been considered crucial in the understanding about the origins of life. It has been described as the most significant trigger that engendered a mutualistic behavior between nucleic acids and peptides, allowing the emergence of biological systems.

Mutational characterization and mapping of the 70S ribosome active site
03 February 2020
https://academic.oup.com/nar/article/48/5/2777/5721209
The ribosome's active site accurately and efficiently processes α-amino acid monomers using catalytic rRNA, that we would expect to exhibit high levels of conservation and would be less permissible, or flexible, to mutation. In fact, previous work has demonstrated in vivo that many nucleotide changes to highly-conserved nucleotides are detrimental , but the ribosome can still withstand some changes at select positions

As expected, the entire PTC active site (PTC-ring, A-loop, and P-loop) exhibited a high-level of conservation, with ∼75% of the nucleotide positions possessing a Shannon Entropy value at or near zero.

My comment: This is hard evidence, that a stepwise, gradative evolution of the Peptidyl Transferase Center is not supported by the empirical data provided in this paper.

Claim: The emergence of this proto-PTC is a prerequisite to couple a chemical symbiosis between RNAs and peptides that further evolved both to (i) become the large subunit of the ribosome by the principle of accretion and (ii) to allow the emergence of the genetic code. Its importance cannot be challenged as it composes the central core of the decoding language of biology.
Reply: There is no selection pressure why  this highly complex system would/should emerge without the genetic code, and vice versa. 

Claim: Caetano-Anollés and Sun used structural analyses to provide evidence that tRNAs were older than ribosomes and were coopted to operate in the translation machinery.
Reply: Before the translation machinery can operate, ALL essential players must be fully formed an in place. In the same sense, as an automobile can only fulfill its function, if all parts are working together once fully formed, constituting a device of integrated complexity, the same is the case for the ribosome, where , if even one tiny peace is missing, nothing goes. Imagine, you have a fully operational translation machinery, and instead of all aminoacyl tRNA synthetases are present, what would happen? The entire translation process would absolutely brake down, and any polypeptide product would be non-functional, and not fold into functional 3D forms. 

Claim: Farias et al. reconstructed a 3D structure of the PTC based on an ancestral sequence of tRNAs and observed a structural similarity of 92% when compared to the PTC of the bacteria Thermus thermophilus. Together, all these data make evident a scenario for the origin of life in which an evolutionary and chronological connection can be observed between these two essential components of the translation system: tRNAs and rRNAs.
Reply: This makes no sense whatsoever. How do they make the jump from the evidence to the conclusion? How would PTC and tRNA's come to a functional relationship and organization without all other players in place, and the genetic code set up? 

Observation: Besides, as we were interested in understanding the relevance of the PTC to the early origin of life, we decided to exclude eukaryotic sequences from the analyses. Eukaryotes are now known to have originated from archaeal organisms coming from the phylum Lokiarchaeota, subphylum Asgard, therefore being derivate clades and having no substantial role in early origins of life
Reply: The authors implicitly admit that there is no homologous sequence of the eukaryotic and prokaryotic ribosome. This is a deal killer form common ancestry ( and there are many other points relevant to this observation, listed later )

Translation through ribosomes,  amazing nano machines - Page 2 Peptid10

Claim: The entire concept for the irreducibly complex ribosome is only wishful thinking. From your answer, it is clear that you don't know what you are talking about. Here is the evidence that in order to have peptide synthesis you need only short RNA. Also, I'm sending the 2012 and 2016 Anolles papers where is presented IN DETAILS loop by loop, helix by helix entire evolution of the ribosome. You can see that the ribosomal RNA and tRNA are coevolved EXACTLY as suppose to be according to step by step evolutionary development. ALL DATA CLEARLY SUGGESTS THAT THE RIBOSOME IS NOT IRREDUCEBLY COMPLEX. Your hypothesis for SUDDEN ID dependent formation is NOT supported at all. Please do not answer unprepared and after all, please acknowledge the data even that contradicts your view.


Response: Handwaving the claim away and glossing over will not solve the point in question, and refute the made observation. If abiogenesis researchers want to be taken seriously, they need to address the objections in a consistent manner, and if a threshold is reached, where natural mechanisms don't suffice, or conceptual problems are pointed out that cannot be overcome, than it is expected that they acknowledge the status quo, and the facts presented. Observing and reasoning about the many intricate patterns in nature requires that one is able to recognize the boundaries of what unguided, random, non-intelligent mechanisms can achieve, and when complexity is observed in the natural world that implodes that range, design should be expected to be inferred as the more case adequate explanation. As we see today, science is unravelling more and more biomechanical complexity, and multilayered information systems working conjoined and in a teamwork.  Unfortunately, as it seems, rarely evolutionary biologists are open-minded enough to do so because evolutionary scenarios are ingrained in their thinking from young age and through education, so giving a second thought on the matter is usually not on the table, but evolutionary assertions are asserted over and over, and considered as the only viable and acceptable scenario, while intelligent design is derisen and ridiculed as unscientific, and incredulity is in most cases the only answer.

Fact remains, that translation ONLY works with all parts involved working in an integrated fashion together, in a joint venture.

According to Darwins Theory, the mechanism of natural selection is survival of the fittest. Leaving the fact on side, that there was no life when the Ribosome emerged, ( life depends on the ribosome, andself-replication), the question is:

1. What function would each of the following molecules have on their own?

1. The Ribosome
Conserved nucleotides in the peptidyl-transferase center (PTC) and its proximity may play a key role in peptide-bond formation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592644/
2. Aminoacyl -tRNA synthetases
3. tRNA's
4. mRNA
5. A SELECTED pool of 20 amino acids ( as used in life, from hundreds supposedly existing on early earth )

The functionality of translation would not be maintained  after any of the listed parts have been removed. I would go a step further and say, that even changing a few amino acids or ribonucleotides near the peptidyl transferase center, and the entire translation system would absolutely break down.

Claim:The Origin of Prebiotic Information System in the Peptide/RNA World: A Simulation Model of the Evolution of Translation and the Genetic Code 2019 Mar 1
This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: transfer RNAs (tRNAs), aminoacyl-tRNA synthetase (aaRS), messenger RNAs (mRNAs), ribosomes, and various enzymes. When assembled in the right order, the translation machine created proteins, a process that transferred information from mRNAs to assemble amino acids into polypeptide chains.
Response: How is this not a made-up just so hypothetical scenario that has no real world plausiblity? Why should unguided events lead to hiearchies and emergence at all, rather than racemisation and asphaltization of molecules? The thing is, there's no driver for any of the pieces to evolve individually because single parts confer no advantage in and of themselves. Assembling things in the right order leading to functional integrated machine-like complexity, where    

why would any natural unguided events come up with any of the four molecules, if individually, there would be no function whatsoever for them ? This cannot be pointed out clear enough. 

Soren Lovtrup, professional biologist in Sweden, said
"...the reasons for rejecting Darwin's proposal were many, but first of all that many innovations cannot possibly come into existence through accumulation of many small steps, and even if they can, natural selection cannot accomplish it, because incipient and intermediate stages are not advantageous."

Natural selection would not select for components of a complex system that would be useful only in the completion of that much larger system.
In other words : Why would natural selection select an intermediate biosynthesis product, which has by its own no use for the organism, unless that product keeps going through all necessary steps, up to the point to be ready to be assembled in a larger system ?  Never do we see blind, unguided processes leading to complex functional systems with integrated parts contributing to the overall design goal.
A minimal amount of instructional complex information is required for a gene to produce useful proteins. A minimal size of a protein is necessary for it to be functional.   Thus, before a region of DNA contains the requisite information to make useful proteins, natural selection would not select for a positive trait and play no role in guiding its evolution.

But on top of that: The Ribosome requires over 200 scaffold proteins, chaperones, and 75 cofactors for its assembly. tRNA's also require a very complex biosynthesis pathway. Arguing that natural stepwise, gradual unguided processes produced all these molecular machines resulting in the making of the ribosome which cannot function unless all other parts are there and interconnected, is far from being a reasonable, plausible, and logical assertion and inference. 

Translation is just a small part of the entire irreducible chain to make functional proteins: Each individual of the 25 unimaginably complex holoproteins have only function when everything works together:

The interdependent and irreducible structures required to make proteins
https://reasonandscience.catsboard.com/t2039-the-interdependent-and-irreducible-structures-required-to-make-proteins

To make proteins, and direct and insert them to the right place where they are needed, at least 25 unimaginably complex biosyntheses and production-line like manufacturing steps are required. Each step requires extremely complex molecular machines composed of numerous subunits and co-factors, which require the very own processing procedure described below, which makes its origin an irreducible  catch22 problem:

THE GENE REGULATORY NETWORK "SELECTS" WHEN, WHICH GENE IS TO BE EXPRESSED
INITIATION OF TRANSCRIPTION BY RNA POLYMERASE
TRANSCRIPTION ERROR CHECKING BY CORE POLYMERASE AND TRANSCRIPTION FACTORS
RNA CAPPING
ELONGATION
SPLICING
CLEAVAGE
POLYADENYLATION AND TERMINATION
EXPORT FROM THE NUCLEUS TO THE CYTOSOL
INITIATION OF PROTEIN SYNTHESIS (TRANSLATION) IN THE RIBOSOME
COMPLETION OF PROTEIN SYNTHESIS  
PROTEIN FOLDING
MATURATION
PROTEIN TARGETING TO THE RIGHT CELLULAR COMPARTMENT
ENGAGING THE TARGETING MACHINERY BY THE PROTEIN SIGNAL SEQUENCE
CALL CARGO PROTEINS TO LOAD/UNLOAD THE PROTEINS TO BE TRANSPORTED
ASSEMBLY/DISASSEMBLY OF THE TRANSLOCATION MACHINERY
VARIOS CHECKPOINTS FOR QUALITY CONTROL AND REJECTION OF INCORRECT CARGOS
TRANSLOCATION TO THE ENDOPLASMIC RETICULUM
POSTRANSLATIONAL PROCESS OF PROTEINS IN THE ENDOPLASMIC RETICULUM OF TRANSMEMBRANE PROTEINS AND WATER-SOLUBLE PROTEINS
GLYCOSILATION OF MEMBRANE PROTEINS IN THE ER ( ENDOPLASMIC RETICULUM )
ADDITION OF OLIGOSACCHARIDES
INCORRECTLY FOLDED PROTEINS ARE EXPORTED FROM THE ER, AND DEGRADED IN THE CYTOSOL
TRANSPORT OF THE PROTEIN CARGO TO THE END DESTINATIONS AND ASSEMBLY

Claim: Add a part. Make it necessary. That is the heart of Mullerian two-step process.
Reply: Müller introduced this concept way back in 1918, and did so in the following scientific paper: Genetic Variability, Twin Hybrids and Constant Hybrids in a Case of Balanced Lethal Factors by Hermann Joseph Müller, Genetics, 3(5): 422-499 (1918)

Here is the relevant quote :

Most present-day animals are the result of a long process of evolution, in which at least thousands of mutations must have taken place. Each new mutant in turn must have derived its survival value from the effect upon which it produced upon the 'reaction system' that had been brought into being by the many previously formed factors in cooperation; thus, a complicated machine was gradually built up whose effective working was dependent upon the interlocking action of very numerous different elementary parts or factors, and many of the characters and factors which, when new, were originally merely an asset finally became necessary. 

Reply: The problem is always explaining how biological information or function is built up in the first place.

First paper linked in the email by Dimiter: 
Ribosomal proteins as documents of the transition from unstructured (poly)peptides to folded proteins

As a first part of my reply, here to the lucid parts of the paper which partially agree with:
Observation: Most peptides, even those composed of the 20 proteinogenic amino acids, are of no structural and functional use to RNA, placing a premium on synthesizing only useful forms and passing the information on to the next generation. Given the broad spectrum of steps needed to fulfill even the basic requirements of an information-bearing chemical system capable of autocatalytic replication, it seems clear that the RNA-peptide world must have achieved considerable complexity well before its transition to the DNA-protein world we observe today. In making this transition, the RNA-peptide world faced a considerable challenge: whereas the chemistry of the RNA-to-DNA transition seems unproblematic (Ritson and Sutherland, 2014), there is a major obstacle on the path from peptides to proteins, known as the protein folding problem.
Reply:  Origin and Evolution of DNA and DNA Replication Machineries 
https://www.ncbi.nlm.nih.gov/books/NBK6360/
Scientists are struggling to answer major questions such as: how did the DNA/Protein world come about, why would such partition of tasks evolve in the RNA world, and which came first, DNA or Protein? Again, we find the ‘chicken and egg’ problem.

Ribonucleotide reductase (RNR) which are the main player in the transition from RNA to DNA are ENORMOUSLY COMPLEX proteins. It takes these enzymes to make DNA. But it takes DNA to make these enzymes. What came first?

From RNA to DNA impossible
https://reasonandscience.catsboard.com/t1784-from-rna-to-dna-impossible

Formation of Deoxyribonucleotides
https://reasonandscience.catsboard.com/t2028-the-dna-double-helix-evidence-of-design#3432

The protein folding problem from an evolutionary perspective
Protein structure, in contrast, is an altogether more complex property and the process by which proteins reach their structure (folding) is easily disrupted and readily undone by even minor changes in temperature or the chemical environment. Once denatured, proteins tend to aggregate and can either not be renatured, or only with large loss of material, making denaturation a substantially irreversible process. The easy loss of structure in most proteins is due to the low free energy of folding (often equivalent to just a few hydrogen bonds), which places them energetically close to the unfolded state. Their tendency to aggregate upon denaturation is due to the dominant role of the hydrophobic effect in folding, which leads folded proteins to mainly segregate hydrophobic residues to the protein core and hydrophilic residues to the surface. When the hydrophobic residues of the core become exposed in the denatured state, they tend to coalesce into heterogeneous tangles, which are generally impossible to resolve and must be degraded. The closeness of the structured and unstructured states in most proteins and the many problems arising to living beings from this are documented in the elaborate protein quality control and degradation systems that are universal to life

Forces Stabilizing Proteins - essential for their correct folding
https://reasonandscience.catsboard.com/t2692-forces-stabilizing-proteins-essential-for-their-correct-folding

Even biophotons!! are involved in protein folding: 
The mechanism and properties of bio-photon emission and absorption in protein molecules in living systems
https://aip.scitation.org/doi/10.1063/1.4709420

Quantum mechanic communication in cells: A paradigm shift in biology
https://www.youtube.com/watch?v=9x32MF79AkA
https://reasonandscience.catsboard.com/t3021-awe-inspiring-biophoton-cell-cell-communication-points-to-design#7981

Claim: Proteins from peptides: The staggering size of protein sequence space and the low incidence of folded exemplars within it essentially preclude an origin of folded domains by random concatenation of amino acids. An alternative scenario proposes that the first folded domains did not arise from random processes, but from the increased complexity of the peptides that had evolved in the RNA world
Reply: This is an entirely UNSUPPORTED claim. 

No evidence that RNA molecules ever had the broad range of catalytic activities
https://reasonandscience.catsboard.com/t2243-no-evidence-that-rna-molecules-ever-had-the-broad-range-of-catalytic-activities

The origin of replication and translation and the RNA World
https://reasonandscience.catsboard.com/t2234-the-origin-of-replication-and-translation-and-the-rna-world
The replicase itself is produced by translation of the respective mRNA(s), which is mediated by the immensely complex ribosomal apparatus. Hence, the dramatic paradox of the origin of life is that, to attain the minimum complexity required for a biological system to start on the Darwin-Eigen spiral, a system of a far greater complexity appears to be required. How such a system could evolve is a  puzzle that defeats conventional evolutionary thinking, all of which is about biological systems moving along the spiral; the solution is bound to be unusual.

Claim:For the most part, contemporary proteins can be traced back to a basic set of a few thousand domain prototypes, many of which were already established in the Last Universal Common Ancestor of life on Earth, around 3.5 billion years ago. 
Response:  Common descent, the tree of life, a failed hypothesis
https://reasonandscience.catsboard.com/t2239-evolution-common-descent-the-tree-of-life-a-failed-hypothesis

1. The DNA replication machinery is not homologous in the 3 domains of life. The bacterial core replisome enzymes do not share a common ancestor with the analogous components in eukaryotes and archaea.
2. Bacteria and Archaea differ strikingly in the chemistry of their membrane lipids. Cell membrane phospholipids are synthesized by different, unrelated enzymes in bacteria and archaea, and yield chemically distinct membranes.
3. Sequences of glycolytic enzymes differ between Archaea and Bacteria/Eukaryotes. There is no evidence of a common ancestor for any of the four glycolytic kinases or of the seven enzymes that bind nucleotides.
4. There are at least six distinct autotrophic carbon fixation pathways. If common ancestry were true, an ancestral Wood–Ljungdahl pathway should have become life's one and only principle for biomass production.
5. There is a sharp divide in the organizational complexity of the cell between eukaryotes, which have complex intracellular compartmentalization, and even the most sophisticated prokaryotes (archaea and bacteria), which do not.
6. A typical eukaryotic cell is about 1,000-fold bigger by volume than a typical bacterium or archaeon, and functions under different physical principles: free diffusion has little role in eukaryotic cells but is crucial in prokaryotes
7. Subsequent massive sequencing of numerous, complete microbial genomes have revealed novel evolutionary phenomena, the most fundamental of these being: pervasive horizontal gene transfer (HGT), in large part mediated by viruses and plasmids, that shapes the genomes of archaea and bacteria and call for a radical revision (if not abandonment) of the Tree of Life concept
8. RNA Polymerase differences: Prokaryotes only contain three different promoter elements: -10, -35 promoters, and upstream elements.  Eukaryotes contain many different promoter elements
9. Ribosome and ribosome biogenesis differences: Although we could identify E. coli counterparts with comparable biochemical activity for 12 yeast ribosome biogenesis factors (RBFs), only 2 are known to participate in bacterial ribosome assembly. This indicates that the recruitment of individual proteins to this pathway has been largely independent in the bacterial and eukaryotic lineages. 22


Observation: The origin of these domain prototypes, however, remains poorly understood.
Response: Uncertainty quantification of a primordial ancestor with a minimal proteome emerging through unguided, natural, random events
https://reasonandscience.catsboard.com/t2508-abiogenesis-uncertainty-quantification-of-a-primordial-ancestor-with-a-minimal-proteome-emerging-through-unguided-natural-random-events

The simplest free-living bacteria is Pelagibacter ubique. 13 It is known to be one of the smallest and simplest, self-replicating, and free-living cells.  It has complete biosynthetic pathways for all 20 amino acids.  These organisms get by with about 1,300 genes and 1,308,759 base pairs and code for 1,354 proteins.  14  That would be the size of a book with 400 pages, each page with 3000 characters.  They survive without any dependence on other life forms. Incidentally, these are also the most “successful” organisms on Earth. They make up about 25% of all microbial cells.   If a chain could link up, what is the probability that the code letters might by chance be in some order which would be a usable gene, usable somewhere—anywhere—in some potentially living thing? If we take a model size of 1,200,000 base pairs, the chance to get the sequence randomly would be 4^1,200,000 or 10^722,000


Claim: One hypothesis posits that they arose from an ancestral set of peptides, which acted as cofactors of RNAmediated catalysis and replication.
Response: 
(Big!)problem 1: New technologies to analyse protein function: an intrinsic disorder perspective
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014577/

The corresponding DNA sequences dictate the amino acid sequences. Specific functionality of a given protein is defined by a unique spatial positioning of its amino acid side chains and prosthetic groups, suggesting that such a specific spatial arrangement of functional groups in biologically active proteins is defined by their unique 3D structures predetermined by the unique amino acid sequences encoded in unique genes.

Basic molecules need to polymerize to become information-bearing genomes and proteins with specific functions and come into a functional relationship and interdependence. An organizational structure would have to be established between the domain of information and computation ( the genome and epigenetic information orchestrating gene expression ) and the mechanistic domain, where proteins and enzymes work based on the direction and information flow of the beforementioned blueprint-like information. The puzzle lies with the problem of creating a causal organization, the interrelationship of informational and mechanical aspects into interdependent narratives. One of the challenges of life’s origin is thus to explain how instructional information control systems emerge naturally and spontaneously from mere chemical interactions and start taking over the clever making and control of molecular mechanical dynamics. 
In modern cells, to make proteins, at least 25 unimaginably complex biosyntheses and production-line like manufacturing steps through large multimolecular machines are required. Each step requires exquisitely engineered molecular machines composed of an enormous number of subunits and co-factors, which require the very own processing procedure described, which makes its origin an irreducible  catch22 problem.

Problem 2: Peptide Bond Formation of amino acids in prebiotic conditions: another unsurmountable problem of protein synthesis on early earth
https://reasonandscience.catsboard.com/t2130-peptide-bonding-of-amino-acids-to-form-proteins-and-its-origins#6664

The Role of Lipid Membranes in Life’s Origin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370405/
A plausible mechanism for synthesis of peptide bonds and ester bonds on the prebiotic Earth continues to be a major gap in our understanding of the origin of life.

Peptides by Activation of Amino Acids with CO on (Ni,Fe)S Surfaces: Implications for the Origin of Life
Claudia Huber and Guenter Waechtershaeuser
Under the dilute aqueous conditions most relevant for the origin of life, activation of the amino acids by coupling with hydrolysis reactions notably of inorganic polyphosphates has been suggested. It is, however, not clear how under
hot aqueous conditions such hydrolytically sensitive coupling compounds, if geochemically available at all, could resist rapid equilibration.
http://fire.biol.wwu.edu/cmoyer/zztemp_fire/biol345_S99/huber2.pdf


Problem 3:  the prevalence of protein sequences adopting functional enzyme folds.
Combined with the estimated prevalence of plausible hydropathic patterns (for any fold) and of relevant folds for particular functions, this implies the overall prevalence of sequences performing a specific function by any domain-sized fold may be as low as 1 in 10(77), adding to the body of evidence that functional folds require highly extraordinary sequences.
https://www.ncbi.nlm.nih.gov/pubmed/15321723?fbclid=IwAR2WqQIOoD3Opw1tmhd6Z5K76yAcJ-w_DbwlWnPml5jVxM34YxC9l7N3PHw

Chemical evolution of amino acids and proteins ? Impossible !!
https://reasonandscience.catsboard.com/t2887-chemical-evolution-of-amino-acids-and-proteins-impossible

Claim: Initially, these peptides were entirely dependent on the RNA scaffold for their structure, but as their complexity increased, they became able to form structures by excluding water through hydrophobic contacts, making them independent of the RNA scaffold.
Reply: How does the author know that there were RNA scaffolds on prebiotic earth?

Claim: ability to fold was thus an emergent property of peptide-RNA coevolution. The ribosome is the main survivor of this primordial RNA world and offers an excellent model system for retracing the steps that led to the folded proteins of today, due to its very slow rate of change. Close to the peptidyl transferase center, which is the oldest part of the ribosome, proteins are extended and largely devoid of secondary structure; further from the center, their secondary structure content increases and supersecondary topologies become common, although the proteins still largely lack a hydrophobic core; at the ribosomal periphery, supersecondary structures coalesce around hydrophobic cores, forming folds that resemble those seen in proteins of the cytosol. Collectively, ribosomal proteins thus offer a window onto the time when proteins were acquiring the ability to fold.
Reply: These are unsupported claims.

Observation: It seems impossible that this elaborate interplay of complex macromolecules could have emerged de novo from abiotic processes
Reply: ABSOLUTELY AGREED. 

Claim: it is generally accepted that life must have started in a simpler form, which has been the subject of much theorizing and some experimentation. Among the possibilities considered, by far the most popular and best supported has been that of RNA forming the first systems capable of autocatalytic replication, acting as both the information bearer and the agent of catalysis. The RNA world is now well established and
widely considered to have been the direct precursor to the DNAprotein world of today.
Reply: The problem of the origin of the hardware and software in the cell is far greater than commonly appreciated
https://reasonandscience.catsboard.com/t2997-the-problem-of-the-origin-of-the-hardware-and-software-in-the-cell-is-far-greater-than-commonly-appreciated

The very origin of the first organisms presents at least an appearance of a paradox because a certain minimum level of complexity is required to make self-replication possible at all; high-fidelity replication requires additional functionalities that need even more information to be encoded.  The crucial question is how the Darwin-Eigen cycle could have started—how was the minimum complexity that is required to achieve the minimally acceptable replication fidelity attained? In even the simplest modern systems, such as RNA viruses, replication is catalyzed by complex protein polymerases. The replicase itself is produced by translation of the respective mRNA(s), which is mediated by the immensely complex ribosomal apparatus. Hence, the dramatic paradox of the origin of life is that to attain the minimum complexity required for a biological system to start on the Darwin-Eigen spiral, a system of a far greater complexity appears to be required. How such a system could emerge is a  puzzle that defeats conventional evolutionary thinking, all of which is about biological systems moving along the spiral; the solution is bound to be unusual. The origin of life—or, to be more precise, the origin of the first replicator systems and the origin of translation—remains a huge enigma, and progress in solving these problems has been very modest—in the case of translation, nearly negligible.4

Second paper linked in the email by Dimiter: 
Peptidyl-transferase ribozymes: trans reactions, structural characterization and ribosomal RNA-like features 


Claim: Similar catalytic rates but different primary sequences and different metal ion requirements. One of these ribozymes has now been re-engineered to catalyze intermolecular peptide-bond formation using an aminoacylated nucleotide and an amino-acid-linked oligonucleotide as substrates. Our results demonstrate that a ribozyme can catalyze peptide-bond formation reactions analogous to the action of the ribosome and, most surprisingly, appears to use similar sequence and structure motifs. These findings provide evidence for the feasibility of the 
Reply: The authors confess re-engineering. That means ===>>> Intelligent design !! Case closed. 


Third paper linked in the email by Dimiter:
Could a Proto-Ribosome Emerge Spontaneously in the Prebiotic World? 


Observation: An indispensable prerequisite for establishing a scenario of life emerging by natural processes is the requirement that the first simple proto-molecules could have had a realistic probability of self-assembly from random molecular polymers in the prebiotic world.
Reply: There is more than enough evidence demonstrating that protein synthesis by unguided random events is not possible at all. 
https://reasonandscience.catsboard.com/t2706-main-topics-on-proteins-and-protein-synthesis

Claim: Three concentric structural elements of different magnitudes, having a dimeric nature derived from the symmetrical region of the ribosomal large subunit, were suggested to constitute the vestige of the proto-ribosome. It is assumed to have materialized spontaneously in the prebiotic world, catalyzing non-coded peptide bond formation and simple elongation. 
Reply: The problem of chain termination
https://reasonandscience.catsboard.com/t2130-peptide-bonding-of-amino-acids-to-form-proteins-and-its-origins
To form a chain, it is necessary to react bifunctional monomers, that is, molecules with two functional groups so they combine with two others. If a unifunctional monomer (with only one functional group) reacts with the end of the chain, the chain can grow no further at this end. If only a small fraction of unifunctional molecules were present, long polymers could not form. But all ‘prebiotic simulation’ experiments produce at least three times more unifunctional molecules than bifunctional molecules. Formic acid (HCOOH) is by far the commonest organic product of Miller-type simulations. Indeed, if it weren’t for evolutionary bias, the abstracts of the experimental reports would probably state nothing more than: ‘An inefficient method for production of formic acid is here described …’ Formic acid has little biological significance except that it is a major component of ant (Latin formica) stings.

Observation: Even the sequence of a simple ribozyme of 40 nucleotides has 10^24 possible compositions. To represent all of these compositions at least once, and thus to establish a certainty that this simple ribozyme could have materialized, requires 27 kg of RNA chains, which classifies spontaneous emergence as a highly implausible event.
Reply: We are in FULL AGREEMENT with the observation :=)) 

Observation:  probability of spontaneous occurrence of the DPR sequence, obtained under the notion of limited sequence specificity, may be too optimistic, but even a significantly lower probability is still acceptable, taking into consideration that the emergence of life is believed to have occurred just once. Given optimal, yet unknown environmental conditions and sufficient time, a small pond with a relatively low concentration of random RNA chains of about 70 mer may have provided feasible likelihood for the materialization of a prebiotic apparatus catalyzing non-coded peptide-bond formation and simple elongation. 
Reply: So what is it now? Highly implausible, or feasible likelihood ? The paper is in contradiction with itself !! 

Observation: The first true alternative to terrestrial biology will be found on an extrasolar planet, in a rock from Mars, or within an extreme environment on Earth. More likely, it will be the handiwork of an intelligent species that has discovered the principles of Darwinian evolution and learned to devise chemical systems that have the capacity to generate bits on their own.
Reply: Or maybe a superpowerful intelligent creator was involved ? Seems the most likely scenario to me.

Fourth paper provided by Dimiter: 
History of the ribosome and the origin of translation

Intro: We present a molecular-level model for the origin and evolution of the translation system, using a 3D comparative method. In this model, the ribosome evolved by accretion, recursively adding expansion segments, iteratively growing, subsuming, and freezing the rRNA.
Reply:  When naturalistic explanations are short coming, it is not rare that the authors resort ad-hoc to a "frozen accident". The intro of the paper resorts as well to that "escape", and as such, it is a implicit admission that rational evidence based , plausible and logical explanations are lacking.

Science-based on materialism resorting to frozen accidents.
https://reasonandscience.catsboard.com/t2889-science-based-on-materialism-resorting-to-frozen-accidents

Claim:  Prokaryotic ribosomes evolved in six phases, sequentially acquiring capabilities for RNA folding, catalysis, subunit association, correlated evolution, decoding, energy-driven translocation, and surface proteinization.
Reply: Why should stochastic unguided natural events " evolve" capabilities in a orderly sequenced fashion ? This is streching far too far the capabilities of unguided random chemical reactions!! How is it possible, that the authors are not realizing this VERY OBVIOUS fact? Not only that, but they outline what it is, namely: RNA folding, catalysis, subunit association, correlated evolution, decoding, energy-driven translocation, and surface proteinization. WOW!!! I mean: Really ???!! I mean: How can the authors make such a huge claim, shamelessly, without a blinker of an eye? This is just ad-hoc speculation without a SHRED of evidence to back up the claims. This is not science. This is PSEUDO-SCIENTIFIC hogwash !! How can people not realize this?? 

In regards of the origin of tRNAs: 



Piecemeal Buildup of the Genetic Code, Ribosomes, and Genomes from Primordial tRNA Building Blocks
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198078/

Claim: tRNA is the oldest and most central nucleic acid molecule of the cell. Its co-evolutionary interactions with aminoacyl-tRNA synthetase protein enzymes define the specificities of the genetic code and those with the ribosome their accurate biosynthetic interpretation.
Reply: Why should tRNA's define the genetic code? There is no reason, why unguided events would have selected a set of 20 amino acids, nor their cognate aminoacyl-tRNA synthetases, and even less, that these molecules would have frozen somehow the triplet codon set of RNA's or DNA. Simply said: This is baseless speculation without a shred of evidence to back up the claim. Its a made-up story.

Claim: We propose that these nucleic acid loops were capable of interacting stereochemically with evolving protein structure and responding to their molecular makeup.
Reply: Claiming that proteins are the product of evolution is unsupported. There is no evidence for this.

Claim: Increases in these interactions canalized both the appearance of genetic memory and building blocks (modules) of RNA with which to construct processive biosynthetic machinery on one hand and genomic memory storage on the other.
Reply: One of the challenges of life’s origin is thus to explain how instructional information control systems emerge naturally and spontaneously from mere chemical interactions and start taking over the clever making and control of molecular mechanical dynamics.

1. Whenever there are things that cohere only because of a purpose or function (for example, all the complicated parts of a watch that allow it to keep time), we know that they had a designer who designed them with the function in mind; they are too improbable to have arisen by random physical processes. (A hurricane blowing through a hardware store could not assemble a watch.)
2. The essential parts of a living cell cohere to a functional whole. They are found forming an integrated complex system because they make it possible together for the cell to self-replicate, adapt, and remain alive. There is an organizational structure between the domain of specified complex information that cleverly directs the making all functional parts and controls molecular mechanical dynamics and self-replication.
3. The functional organization which makes chemicals, building blocks, and macromolecules must have a designer who designed the system with the function in mind: just as a watch implies a watchmaker, a machine implies a machine designer, and a factory, a factory maker. Living cell factories full of machines made through the instructional genetic information were not created by human designers. Therefore, living cells must have had a non-human intelligent designer

Transfer RNA, and its biogenesis, best explained through design
https://reasonandscience.catsboard.com/t2070-transfer-rna-and-its-biogenesis

tRNA's are very specific molecules, and the " made of " follows several steps, requiring a significant number of proteins and enzymes, which are often made of several subunits and ainded by essential co-factors and metals.

The challenge for evolution to the fact, that biological systems incorporate several essential parts, that cannot be eliminated without losing the core function of the system in question, and that these parts have no function of their own and could therefore not be product of natural mechanisms, of gradual evolutionary steps, is in my view more severe than most philosophers of science and scientists like Behe exemplify. In systems of enormous biological complexity like the cell, thousands of parts are essential , many more parts, than the well known examples like the flagellum. Irreducibility is found from the highest level of biological organisation and systems, to a single DNA deoxyribonucleotide, which loses function if reduced to its single components, the bases, phosphate or sugar. Just take off one, and the molecule loses its function. Same goes for the cell. Take off one building block, like the spindle apparatus, and mitosis and cell division is not possible, and life could not reproduce itself.

The make of proteins is similar to the make of cars in a car factory. If the grinder machine to make the motor pistons has a mal function, the pistons cannot be finished, the car's motor block cannot be assembled with all parts, and the motor would not function without that essential part. Amongst thousands of parts, just a tiny one will compromise the function of the whole system. In biological nano-factories, the solutions to overcome problems like damage must all be pre-programmed, and the repair "working horses" to resolve the problem must be ready in place and "know" what to do how, and when. If a roboter in a factory assembly line fails, employees are ready to detect the error and make the repair . In the cell, the mal function of any part even as tiny and irrelevant as it might seem, can be fatal, and if the repair mechanisms are not functioning correctly and fully in place right from the start, the repair can't be done, and life ceases. These repair enzymes which cleave, join, add, replace etc. must be programmed in order to function properly right from the start. Aberrantly processed pre-tRNAs for example are eliminated through a nuclear surveillance pathway by degradation of their 3′ ends, whereas mature tRNAs lacking modifications are degraded from their 5′ends in the cytosol. 




1. https://www.frontiersin.org/articles/10.3389/fmolb.2019.00123/full
2. https://pubmed.ncbi.nlm.nih.gov/28454764/



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27Translation through ribosomes,  amazing nano machines - Page 2 Empty Central Dogma & Origin of the Ribosome on Wed Sep 30, 2020 9:47 am

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Central Dogma & Origin of the Ribosome
https://www.youtube.com/watch?v=x2DaEyfN0Ws

The ribosome works like a factory and machine, and requires like a printing machine precisely fitting parts to work together. And those parts cannot be the result of evolution, since individually, those parts confer no function. 

Video comment: life the greatest story ever told life on earth originated about four billion years ago the origin of life was a transition from simple chemistry to complex biochemistry the first branching of the tree of life created bacteria and archaea later a third branch Eukarya split off from archaea
Reply: This claim is falsified alone by the fact that the bacterial ribosome and eukaryotic ribosome are not homologous:

Mutational characterization and mapping of the 70S ribosome active site
03 February 2020
https://academic.oup.com/nar/article/48/5/2777/5721209

Observation: Besides, as we were interested in understanding the relevance of the PTC to the early origin of life, we decided to exclude eukaryotic sequences from the analyses. Eukaryotes are now known to have originated from archaeal organisms coming from the phylum Lokiarchaeota, subphylum Asgard, therefore being derivate clades and having no substantial role in early origins of life
Reply: The authors implicitly admit that there is no homologous sequence of the eukaryotic and prokaryotic ribosome. This is a deal killer form common ancestry ( and there are many other points relevant to this observation, listed later )

Video comment:  polymers are replicated transcribed and translated the rules that govern the information flow during these processes are known as the central dogma of molecular biology the central dogma says that RNA can be replicated to make new RNA. RNA can be reversed transcribed to make DNA. DNA can be replicated to make new DNA. DNA can be transcribed to make RNA and RNA can be translated to make protein. biology contains what we call molecular symbiotic these are different types of polymers that rely entirely on one another RNA is one type of molecular symbiotic RNA is synthesized by protein protein is the other molecular symbiotic protein is synthesized by RNA in every cell of every organism RNA and protein depend on each other for synthesis

Reply: An organizational structure would have to be established between the domain of information and computation ( the genome and epigenetic information orchestrating gene expression ) and the mechanistic domain, where proteins and enzymes work based on the direction and information flow of the beforementioned blueprint-like information. The puzzle lies with the problem of creating a causal organization, the interrelationship of informational and mechanical aspects into interdependent narratives. One of the challenges of life’s origin is thus to explain how instructional information control systems emerge naturally and spontaneously from mere chemical interactions and start taking over the clever making and control of molecular mechanical dynamics.  In modern cells, to make proteins, at least 25 unimaginably complex biosyntheses and production-line like manufacturing steps through large multimolecular machines are required. Each step requires exquisitely engineered molecular machines composed of an enormous number of subunits and co-factors, which require the very own processing procedure described, which makes its origin an irreducible  catch22 problem.

Video comment: the synthesis of protein by the ribosome is called translation the ribosome is the most ancient and universal macro molecular assembly in the biological world the ribosome has a small subunit that reads the mRNA the ribosome also contains a large subunit that links amino acids in the correct sequence

Reply: First, there would have to be the entire pathway starting from the genome, having a genetic code, and information using the genetic code, to store the information in DNA. Secondly , there would have to be the messenger RNA, and the entire pathway including transcription, and the hyper complex holo protein complex that transcribes the information from RNA to messenger DNA. And there would have to exist already the set of 20 amino acids, synthesized and available in the cell for polymerization. This is a simplified explanation, but the entire pathway is in reality immensy complex, and requires a myriad of complex macromolecules and molecular machines. 

The interdependent and irreducible structures required to make proteins
https://reasonandscience.catsboard.com/t2039-the-interdependent-and-irreducible-structures-required-to-make-proteins

Now, EVEN IF we convey that all those things were already fully extant and evolved, linking the right amino acids together in the correct sequence is far from a simple task. It is a very precise, coordinated process which requires the ribosomal subunits to work together in a coordinated and exquisitely controlled process, where also error check and repair is absolutely essential, and a right balance between speed of translation and error rate must be just right. There is no feasible way how the right speed of polymerization of about 20 amino acids per second could be established by trial and error.  

tRNAs deliver amino acids to the ribosome the evolution of the prokaryotic ribosomes was essentially complete by the last Universal common ancestor or Luca

Video comment: Evolution and natural selection  was in play prior DNA replication began, NOT BEFORE:

The logic of chance, page 266
Evolution by natural selection and drift can begin only after replication with sufficient fidelity is established. Even at that stage, the evolution of translation remains highly problematic. The emergence of the first replicator system, which represented the “Darwinian breakthrough,” was inevitably preceded by a succession of complex, difficult steps for which biological evolutionary mechanisms were not accessible . The synthesis of nucleotides and (at least) moderate-sized polynucleotides could not have evolved biologically and must have emerged abiogenically—that is, effectively by chance abetted by chemical selection, such as the preferential survival of stable RNA species.

Functional proteins from a random-sequence library
Anthony D. Keefe & Jack W. Szostak
Functional primordial proteins presumably originated from random sequences
https://molbio.mgh.harvard.edu/szostakweb/publications/Szostak_pdfs/Keefe_Szostak_Nature_01.pdf?fbclid=IwAR0giOg_aZfFRKQALk7CB22nVIx32ShiN0Vp78cwtAYwmwQ_0RJicfxpR1M
The possible mechanisms to explain the origin of life
https://reasonandscience.catsboard.com/t2515-abiogenesis-the-possible-mechanisms-to-explain-the-origin-of-life

The ribosome works like a factory and machine, and requires like a printing machine precisely fitting parts to work together. And those parts cannot be the result of evolution, since individually, those parts confer no function.

Video comment: ribosome is around four billion years old even though it is extremely ancient we have developed methods for reconstructing the evolution of the ribosome in phase one the LSU and SSU both begin as small RNA stem loops folding to stem loops protects the RNA from chemical degradation
Reply: This is smuggling teleology into the argument. There is no urge for matter to prevent itself to degrade!! This is borrowing from a worldview where intent was at play to make the Ribosome. Something, a materialist cannot resort to !! 

Decomposition of Monomers, Polymers and Molecular Systems: An Unresolved Problem 2017 Jan 17
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370405/
It is clear that non-activated nucleotide monomers can be linked into polymers under certain laboratory conditions designed to simulate hydrothermal fields. However, both monomers and polymers can undergo a variety of decomposition reactions that must be taken into account because biologically relevant molecules would undergo similar decomposition processes in the prebiotic environment.

Video comment: in Phase two the LSU our RNA from the peptidyl transferase center the SSU our RNA function is less certain in Phase three the peptidyl transferase center is encased and rigidify and the exit pore is extended into a short tunnel

Reply: The entrance and exit tunnel of the Ribosome are ABSOLUTELY ESSENTIAL in order for the mRNA's, tRNA's, aminoacyl-tRNA-synthetases to get in, and the growing polymerized strand to get out. How did this precise configuration and position be positioned for correct operation? These tunnels require the right size, directing to the peptidyl transferase center, and the right size of the cavity of the PTC, how were they figured out without intelligence ? Random trial and error until the thing was set up right ? Furthermore.

The ribosomal peptidyl transferase center: structure, function, evolution, inhibition
https://pubmed.ncbi.nlm.nih.gov/16257828/
Functions of the two ribosomal subunits are very distinct. The small subunit deals exclusively with an RNA template (mRNA) on which it assembles complementary RNA entities (tRNA anticodons). The large subunit, in contrast, deals primarily with amino acids that are activated by esterification to the tRNA 3 -hydroxyl of the terminal ribose.

Question: Both subunits are performing  absolutely essential distinguished tasks, which are complementary. Both subunits have no function by themselves. If evolutionary processes would be generating these subunits, it would/should be expected that iterative rounds of random mutations and  selection would "discover" new and useful ribozymes & proteins subunits. In this case, that would however not be the case:

Natural selection would not select for components of a complex system that would be useful only in the completion of that much larger system. In other words : Why would natural selection select an intermediate biosynthesis product, which has by its own no use for the organism, unless that product keeps going through all necessary steps, up to the point to be ready to be assembled in a larger system ?  Never do we see blind, unguided processes leading to complex functional systems with integrated parts contributing to the overall design goal. A minimal amount of instructional complex information is required for a gene to produce useful proteins. A minimal size of a protein is necessary for it to be functional.   Thus, before a region of DNA contains the requisite information to make useful proteins, natural selection would not select for a positive trait and play no role in guiding its evolution.

According to following science paper:
The Ancient History of Peptidyl Transferase Center Formation as Told by Conservation and Information Analyses 
https://www.mdpi.com/2075-1729/10/8/134

The PTC has been recognized as the earliest ribosomal part and its origins embodied the First Universal Common Ancestor (FUCA).



 the SSU terminated associate with formation of the central pseudoknot by the end of phase three the LSU and the SSU associate in phase four and the LSU the tunnel is further developed the SSU gains well-defined binding pockets for the T RNAs and phase five the ratcheting system is acquired the genetic code begins to optimize and expand in Phase six the prokaryotic ribosomes is finalized with a fully optimized genetic code the ribosomal surface is an integrated patchwork of RNA and mature ribosomal proteins the ribosome grew by accretion of new RNA on old RNA like nested Russian dolls



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The Ribosomal Peptidyl Transferase Center: Structure, Function, Evolution, Inhibition
https://geneticacomportamento.ufsc.br/files/2013/08/Polacek05-Ribozima-peptidil-transferase.pdf
Claim: In the RNA World, what was the selective advantage for the host to have a proto-ribosome that “learned” to produce peptides and proteins? It is highly unlikely that the first catalyzed polypeptides themselves had any significant enzymatic functions. Noller (2004) therefore proposed that the driving force for the selection of primitive protein synthesis was to enlarge the structural and, hence, functional repertoire of RNA. e the first translation system that produced “functional” peptides did not evolve to pave an exit path out of the RNA world, but rather “aimed at” improving the properties of RNA molecules and ribozymes in the pre-protein world.
Reply: If that were the case, why do we not see this ocurring still today? Why would RNA's "seek" or "aim" to have functions at all, and more, on top of that, enlarge this functional repertoire? Molecules do not have the urge to function, or to become larger, or to complexify. Molecules will simply lay around, and desintegrate, depending on the environmental conditions.

Claim: This concept of ligand-induced RNA conformational changes obviously survived the transition from the RNA World to the contemporary DNA-RNA-protein world and represents the basic principle of riboswitch elements found in certain prokaryal mRNAs 
Reply: This is begging the question. There is no evidence that a transition from RNA to DNA is feasible. The better explanation is that an intelligent designer created the system fully developed, and able to start translation right from the beginning. 

Claim: However, the need for synchronization of the production and assembly of protodomains apparently favored their association (possibly via RNA ligation) into longer RNA molecules
Reply: Molecules do not have the urge to synchronize things. Only intelligent designers with distant goals do so. 

Claim: Higher-order complexes could have been formed that might have added functional diversity and sophistication to such a hypothetical proto-ribosome
Reply: The guesswork and just-so assertions in this paper are astonishing. Could have, might have. What about: Its extremely unlikely that unguided means produce sophisticated higher order complexes, because thats not how random molecules behave ?

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The ribosome’s has highly efficient, or optimal, design features. Ribosomes are comprised of both protein and RNA molecules, and their proteins make up a sizable fraction of the total protein content of many cells. Cells contain many ribosomes, and naturally in order for the cell to duplicate, the ribosomes must be duplicated. This means a lot of protein synthesis must take place, in order to create all the proteins in all the ribosomes.
One way to help alleviate this production problem would be to have yet more ribosomes in the cell. But that would, in turn, create an even greater protein synthesis burden, since even more proteins would be needed for those additional ribosomes. One way to solve this conundrum is to use RNAs in ribosomes rather than proteins, where possible. It is a fascinating problem, and the paper concludes that we can understand the solution not as the result of evolutionary contingencies, but as a solution to a functional need: Rather than being relics of an evolutionary past, the unusual features of ribosomes may reflect an additional layer of functional optimization that acts on the collective properties of their parts. 2

Ribosomes are optimized for autocatalytic production 1
Many fine-scale features of ribosomes have been explained in terms of function, revealing a molecular machine that is optimized for error-correction, speed and control. Here we demonstrate mathematically that many less well understood, larger-scale features of ribosomes—such as why a few ribosomal RNA molecules dominate the mass and why the ribosomal protein content is divided into 55–80 small, similarly sized segments—speed up their autocatalytic production. 

The ribosome doubling time places a hard bound on the cell doubling time, because for every additional ribosome to share the translation burden there is also one more to make . Even for the smallest and fastest ribosomes, it takes at least 6min, and typically much longer, for one ribosome to make a new set of r-proteins and this estimate does not account for the substantial time that is invested in the synthesis of ternary complexes. This bound seems to explain the observed limits on bacterial growth, because ribosomes must also spend much of their time making other proteins, and shows that ribosomes are under very strong selective pressure to minimize the time they spend reproducing. Similar principles might also apply to some eukaryotes, because the ribosomes of eukaryotes are larger and slower. In fact, even organisms in which cell doubling times are not limited by ribosome doubling times would benefit from faster ribosome production, allowing ribosomes to spend more of their time producing the rest of the proteome. This efficiency constraint was recently shown to have broad physiological consequences for cells. 

1. https://www.nature.com/articles/nature22998
2. https://evolutionnews.org/2017/08/national-association-of-biology-teachers-versus-the-ribosome/

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Journey Inside The Cell Start at 1:28
https://www.youtube.com/watch?v=1fiJupfbSpg&feature=emb_title

Next this RNA transcript approaches and passes through a molecular machine called the nuclear pore complex an information recognition device that controls the flow of information in and out of the cell's nucleus now we see the genetic assembly instructions on the messenger RNA approaching and arriving at a two-part chemical factory called a ribosome the site of protein synthesis as the messenger RNA transcript passes through the ribosome the process of translation begins during translation a mechanical assembly line builds a specifically sequence chain of amino acids in accord with the instructions on the transcript these amino acids are transported from other parts of the cell by molecules called transfer RNAs which link specific sequences of bases to corresponding amino acids the sequential arrangement of the amino acids determines the type of protein constructed

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Quantum mechanic glimpse into peptide bond formation within the ribosome shed light on origin of life

https://link.springer.com/article/10.1007/s11224-017-0980-5

On origin of life
The high conservation of the proto-ribosome nucleotide sequence is suggestive of its robustness under diverse environmental conditions and hence hints at its prebiotic origin.

My comment: It is also evidence that a gradual, evolutionary, step-wise evolution of the sequence would be non-functional, and indication, that the Ribosome had to emerge from the start, fully functional and operational, "as is".

The Peptidyl Transferase Center  is located within an RNA apparatus, which possesses all of the capabilities required for peptide bond formation, it may be a vestige of the prebiotic world. Hence, we proposed that this conserved pocket-like region is a vestige of a prebiotic bonding entity, around which life has evolved. Hence, it seems that this is the primordial ribosome, and called the B proto-ribosome^. This seemingly remnant of the prebiotic era is still functioning in the heart of all of the contemporary ribosomes. The structure of this pocket, which seems to be ingeniously built for accommodating the 3′ ends of the A- and P-site tRNAs

The preservation of RNA activity in performing the extremely important process of genetic code translation indicates that RNA is capable of handling the complexity of the current cellular life, which requires a highly controlled sophisticated regulatory mechanism. Obviously, translation is much more complicated than accidental peptide bond formation. 

Remarkably, within the contemporary ribosomes, the distances between the regions involved in ribosome’s function are far beyond the possibility of any direct Bchemical talk^ (70–140 A). The symmetrical region is located at the heart of the ribosome and chemically connects to all of the ribosome functional centers involved in translation. Hence, it can transmit signals between them. 

This machinery is consistent with the idea that positioning of the reactive groups is the critical factor for catalysis, but does not exclude assistance from ribosomal or substrate moieties. Hence, by offering the frame for correct substrate positioning, as well as for catalytic contribution of the P-site tRNA 2′-hydroxyl group, it became evident that the ribosomal architectural frame governs the positional requirements and provides the means for substrate-mediated chemical catalysis.

There is a notion of the existence of an apparatus that could serve as the proto-ribosome, hypothesized to be a Bpocket-like^ RNA pseudo dimer that is capable of peptide bond formation, peptidyl transfer, and its elongation. Furthermore, the detection of similar twofold symmetryrelated regions in all known structures of the large ribosomal subunit not only indicates the universality of this mechanism but also emphasizes the significance of the ribosomal template for the precise alignment of the substrates as well as for accurate and efficient translocation.

The transition state for formation of the peptide bond in the ribosome
https://www.pnas.org/content/103/36/13327

Using quantum mechanics and exploiting known crystallographic coordinates of tRNA substrate located in the ribosome peptidyl transferase center around the 2-fold axis, we have investigated the mechanism for peptide-bond formation. The calculation is based on a choice of 50 atoms assumed to be important in the mechanism. We used density functional theory to optimize the geometry and energy of the transition state (TS) for peptide-bond formation.

The peptidyl transferase center (PTC), which is located at the depth of a cavity built primarily of ribosomal RNA. This cavity provides the remote interactions dominating initial substrate positioning with stereochemistry suitable for the motions associated with peptide-bond formation and nascent-chain elongation.  Despite the ribosome’s overall asymmetric structure, a sizable 2-fold symmetry-related region, relating RNA backbone fold and nucleotide orientations, rather than nucleotide sequence identities, was revealed around the PTC in all known ribosomes structures. The symmetry-related region contains ≈180 nt and extends far beyond the PTC. It connects all functional centers involved in amino acid polymerization, including peptide-bond formation, the focus of this article. This ribosomal elaborate architectural design guides the process of peptide-bond reaction by forcing a rotational motion consistent with the 2-fold rotation axis. The bond connecting the universally conserved single-strand tRNA–3′ end with the tRNA-acceptor stem of the A-site tRNA almost coincides with the symmetry axis, indicating that A- to P-site translocation involves two synchronized motions: an overall mRNA/tRNA sideways shift and a rotation of the tRNA 3′end. Guided by PTC components, the rotatory motion facilitates peptide-bond formation and nascent-chain elongation. Furthermore, this motion places the A-site nucleophilic amine and the P-site carbonyl carbon at a distance allowing for interactions with the P-site tRNA A76 O2′ throughout a significant part of the rotatory motion, consistent with its suggested participation in peptide-bond formation catalysis. The nascent proteins are directed by the rotatory motion into the exit tunnel at extended conformation, fitting the tunnel’s narrow opening. Hence, the ribosomal architecture provides all of the positional elements required for amino acid polymerization.

Paramount are the energetics of the formation of the transition state (TS), which governs the formation of the peptide bond. Here we show that we have been able to define a quantum mechanical transition state TS that is relevant to peptide-bond formation within the ribosome, characterize both its geometry and energy, and implicate these properties to events associated with peptide-bond formation and polypeptide elongations.

The key geometrical parameters of TS formation are summarized in Table 1, and Fig. 1 shows the image of the optimized TS geometry for the formation of the peptide bond in the ribosome.

Translation through ribosomes,  amazing nano machines - Page 2 Riboso22
Optimized peptide bond TS in the ribosome.
An initial geometry was obtained using the coordinates of ASM in D50S at the A site and its derived P-site tRNA. The amino acid of ASM was converted to alanine.

The optimized TS bond distances are labeled according to whether they are in the act of breaking or forming, to achieve the transition from reactants to products. The end result is that the peptide bond NTranslation through ribosomes,  amazing nano machines - Page 2 Inline-graphic-1 C is formed, which leads to elongating the nascent protein. The new OTranslation through ribosomes,  amazing nano machines - Page 2 Inline-graphic-2 H bond, which is formed on the P-site tRNA, saturates the open valence of the oxygen atom that would occur as the CTranslation through ribosomes,  amazing nano machines - Page 2 Inline-graphic-3 O bond breaks to allow release of the amino acid transferred to the nascent protein. The remaining bond that is breaking in the TS, namely, NTranslation through ribosomes,  amazing nano machines - Page 2 Inline-graphic-4 H, completes the release of the P-site tRNA. Hence, simultaneously with bond making and breaking, the former A-site tRNA can occupy the P site, which becomes available by the former P-site tRNA release.

Notably, the TS fits perfectly into the space available for the rotating A-site 3′ end, provided by the ribosome nucleotide surroundings within the ribosomal PTC (called here the “rotatory space”), after a 45° rotation of the A-site tRNA 3′ end toward the P site

Translation through ribosomes,  amazing nano machines - Page 2 Riboso23
The TS position within the volume occupied by the rotatory motion in the PTC of the ribosome.
(a) A schematic presentation of the combined linear and rotational motions involved in the passage of the A-site tRNA from the A site to the P site. The 2-fold symmetry axis is shown in red. The apparent overlap of the two tRNA stems is a result of the specific view (diagonal toward the back of the paper plane), chosen to show best the concerted motions.
(b) The approximately orthogonal view of the rotatory motion shown in a, looking approximately down the 2-fold symmetry axis, together with the TS, formed after 45° rotation (A site to P site) within the PTC of the ribosome. The transparent cyan “cloud” shows the entire rotatory space, as was simulated every 15° of the rotation. The ribosomal nucleotides are shown in gray. Those below the rotatory space are shown in lighter gray. The TS is shown in dark red. Nucleotides A2602 and U2585 are colored purple and yellow, respectively. Note the marked fit between the TS position and the space provided by the ribosome.
(c) Two views perpendicular to the 2-fold rotation axis. Shown are ends of tRNAs molecules at the P site (green), the A site (blue), the 2-fold axis (red), the TS (dark red), and the nucleotides C2452 and U2585 (gray). The TS lies at its best position between the A- and P-site tRNAs. (Left) View from the subunit interface. (Right) View from the PTC rear wall.

In all respects, it makes good chemical sense, in terms of formation of a peptide bond, the translocation of A-site tRNA to the P site, and P-site tRNA separation from the elongated chain. The chemical sense, after the mathematical criteria, is what corroborates the TS.  The TS is characterized mathematically by normal mode frequencies that are all positive, except for exactly one, which is negative, and corresponds to a vibration along the reaction coordinate sending the old reactants into the new products.

Quantum-Mechanical Study on the Mechanism of Peptide Bond Formation in the Ribosome
https://sci-hub.st/https://pubs.acs.org/doi/full/10.1021/ja209558d

Interactions between active site residues and the 2′-OH are pivotal in orienting substrates in the active site for optimal catalysis. A second 2′-OH group  was identified to be crucial for peptide bond formation, namely that of A2451. The 2′- OH of A2451 was shown to be of potential functional importance.

The ribosome promotes the reaction of the amino acid condensation by properly orienting the reaction substrates.

Energy-dependent protein folding: modeling how a protein folding machine may work
https://www.biorxiv.org/content/10.1101/2020.09.01.277582v2.full.pdf

Here we consider the possibility that protein folding in living cells may not be driven solely by the decrease in Gibbs free energy and propose that protein folding in vivo should be modeled as an active energy-dependent process. The mechanism of action of such protein folding machine might include direct manipulation of the peptide backbone. 

Considering the rotating motion of the tRNA 3’-end in the peptidyltransferase center of the ribosome, it is possible that this motion might introduce rotation to the nascent peptide and influence the peptide’s folding pathway in a way similar to what was observed in our simulations.

We performed molecular dynamics simulations in which a standard force field was augmented by the application of external mechanical forces to the polypeptide backbone. We compared these simulations to control runs without any additional external forces. The directional rotation of the Cterminal amino acid with simultaneous restriction of the movements of the N-terminal amino acid facilitated the formation of native structures in five diverse alpha-helical peptides, confirming that such constraints can have significant consequences for folding dynamics. Strikingly, application of mechanical force accelerated the folding of P4, a fragment of an on-pathway folding intermediate of the well-studied villin headpiece domain HP35, which is one of the fastest-folding protein domains known. The several-fold increase in the rate of P4 folding that was achieved in our experiments seems to suggest that the postulated “physical limit of folding” of HP35 as a whole could be overcome by a protein folding machine. The other four peptides in our experiments likewise attained their alpha-helical structure in the presence of the rotating force, but did not reach their native conformations when allowed to fold unassisted, even though we ran the control unassisted simulations for ~10 times longer than the simulations that included the application of the external force. Some of those peptides might take a very long time to reach their native conformations without application of an external force, whereas others might never fold unassisted, if their unfolded states are more stable than the folded conformations.

The 3’ terminus of the tRNA in the Asite of the ribosome peptidyl transferase center turns by nearly 180 degrees in every translation elongation cycle. Only a 45-degree swing is necessary to achieve the proper stereochemistry of the peptide bond formation; the function of the remaining portion of the turn is unknown, and we have hypothesized that it may be needed to facilitate co-translational folding

These results are in line with our protein folding machine hypothesis. They also support a hypothetical mechanism through which the machine would directly alter the conformations of proteins by applying mechanical force to the peptide backbone.  In vivo the peptide backbone can be manipulated into conformations that cannot be reached without assistance because they are either thermodynamically unstable or kinetically inaccessible. The results of our simulations thus demonstrate the feasibility of a protein folding machine. Some recently published results, including studies of the role of the exit tunnel in nascent chain folding

My comment: This demonstrates that protein folding ( which is essential to get functional proteins ) is a complex, finely orchestrated process that depends not only on the correct amino acid sequence, and the decrease in Gibbs free energy, but also an active energy-dependent process. The mechanism of action of the Ribosome protein folding machine  includes direct manipulation of the peptide backbone. To consider is the rotating motion of the tRNA 3’-end in the peptidyltransferase center of the ribosome. This motion introduces rotation to the nascent peptide which turns by nearly 180 degrees in every translation elongation cycle, and not only a 45-degree swing sufficient to achieve the proper stereochemistry of the peptide bond formation. That additional rotation seems to influence the peptide’s folding pathway in a way similar to what was observed in the simulations performed by the authors of above paper. 

The ability of any present-day protein to fold in isolation and without assistance not shared by most  proteins. Thus, the notion of an active, energy-dependent protein folding mechanism  in vivo reinforces the understanding of an intelligently bioengineered process  than the generally accepted evolutionary process, and that the ability of proteins to attain their native conformations must have evolved by natural selection of sequences that fold quickly and correctly (“evolution solved the protein folding problem” ) becomes more and more remotely possible. 

Cotranslational Protein Folding inside the Ribosome Exit Tunnel
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571824/

For small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins. That the small zinc-finger domain ADR1a folds cotranslationally as the tether connecting it to the ribosome grows in length from ∼20 to ∼30 residues.  ADR1a buried deep in the vestibule of the exit tunnel, provides a clear demonstration that small proteins or protein domains can fold within the ribosome, as predicted by computational studies Although the zinc finger is one of the smallest independently folding protein domains, it has been estimated that ∼9% of all structural domains found in the PDB are less than 40 residues long, and ∼18% are less than 60 residues long. Folding of protein domains wholly or partly inside the exit tunnel may thus be not too uncommon, despite its relatively constrained geometry. 

Mutational analysis of protein folding inside the ribosome exit tunnel
https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.12504
The Ala scanning results are entirely consistent with in vitro studies of purified ADR1a: the residues most critical for stabilizing the folded state are the four Zn2+‐coordinating residues, and residues F12 and L18 that constitute the hydrophobic core.








Translation through ribosomes,  amazing nano machines - Page 2 Riboso24
Visualization by Cryo-EM of the ADR1a Domain in a Stalled Ribosome-ADR1a-SecM (Ms-Sup1; L = 25) Complex
(A) Schematic of the construct used for in vitro translation (top) and cryo-EM reconstructions of stalled E. coli ribosome-SecM-ADR1a complexes (left). The 30S subunit is depicted in yellow, the 50S subunit in gray, and the peptidyl-tRNA with the nascent polypeptide chain in green. Additionally, a cross-section through the cryo-EM density is shown in which the density for the nascent chain and the ADR1a domain (PDB: 2ADR) are depicted in green and red, respectively. A close-up of the tunnel and a schematic view are shown with the structure of the ADR1a domain fitted as rigid body depicted in red.
(B) Isolated density for the ADR1a domain (red) shown at different contour levels (top) compared with corresponding densities calculated from the NMR-derived molecular model of ADR1a (middle). Isolated cryo-EM density is shown transparent with the docked model (red) and the coordinated Zn2+ ion in yellow (bottom).

Protein refolding by the chaperones of the HSP70 family, may be also interpreted as evidence of protein folding in vivo being an active process

Realistic narratives of protein folding must therefore take into account the presence of a several exquisitely and masterfully planned molecular mechanisms that induce external forces and promote correct protein folding.

All living things rely on ribosomes, indicating that they must have been present when life began. Looking closely at the active site of the ribosome, where new proteins are built, the structure reveals that the machinery is composed of RNA, and a particular RNA base performs the reaction

Translation through ribosomes,  amazing nano machines - Page 2 Riboso29
Active site of the ribosome. 
This structure includes a ribosome with the tips of two transfer RNA molecules ( magenta and blue spheres ) bound in the protein-building site. The ribosome nucleotide shown in red catalyzes the reaction



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32Translation through ribosomes,  amazing nano machines - Page 2 Empty My response (Otangelo) to Dimiter on Sat Oct 03, 2020 9:37 am

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My response (Otangelo) to Dimiter

Dimiter: Hello, look carefully, where did you see “no homologous sequence of the eukaryotic and prokaryotic ribosome”. Your interpretation of the claim in the paper is in your way, but it not what the authors say. There is sequence homology in some more and some less and this is normal to explain from the evolutionary model. But let’s go to a more fundamental problem: THE MODEL
Reply: Ok. But there ARE particles that are not homologous, like the 5.8S RNA which is unique to eukaryotes

Eukaryotic Protein Synthesis Differs from Prokaryotic Protein Synthesis Primarily in Translation Initiation
https://www.ncbi.nlm.nih.gov/books/NBK22531/

Questioning that so many differences could be explained by evolutionary means is more than justified.

Otangelo: it is the answer to Caetano-Anollés: “Before the translation machinery can operate, ALL essential players must be fully formed and in place. In the same sense, as an automobile can only fulfill its function, if all parts are working together once fully formed, constituting a device of integrated complexity, the same is the case for the ribosome, where, if even one tiny piece is missing, nothing goes. Imagine, you have fully operational translation machinery, and instead of all aminoacyl tRNA synthetases are present, what would happen? The entire translation process would absolutely break down, and any polypeptide product would be non-functional, and not fold into functional 3D forms
Dimiter: This is fundamentally wrong. I’m surprised that after so many hours spent together explaining how the evolution functions and how the biological systems may be reduced in some conditions and how reduced variants make sense in a more simple system, you continue to put the same an argument over and over again and again.

Reply: Yes, you keep saying that. I gave a closer look at your paper ( see a short review below), and there are good reasons why I am not convinced that your claims are rational and justifiable. We are dealing with the origin of probably THE most complex macromolecular factory in the cell, central to explain the origin of life. 

Otangelo: Look your sentence “Before the translation machinery can operate, ALL essential players must be fully formed and in place.” 
Dimiter: OK, who says that? 
Reply: The relevant question is not WHO says it, but if the evidence points to that direction. I think it does. For example:

The elongation phase of the ribosome-catalyzed translation requires:
1. mRNA
2. a complete set of tRNA's 
3. elongation factor EF-Tu complexed with GTP 
4. a complete set of aminoacyl-tRNA's 
5. elongation factor EF-G dependent on GTP

If ANY of those players is missing, elongation cannot occur. Demonstrate how ANY of the individual molecules would have functions on their own, and explain why, for what reasons, unguided random events would evolve them. 

Dimiter: It comes from your model, not mine
Reply: Your evolutionary model is not true by default. You need to DEMONSTRATE why a down-up approach is conceptually feasible and compelling. Just asserting that it is a better approach than intelligent design based on a preconceived engineering model depending on intelligent action is not enough. 

Dimiter: your pre-set thinking from your irreducible fantasy. I spend enough time explaining that the very first event during the formation of Darwinian evolution was the formation of primitive translation, not the other way around.
Reply: Correct. I appreciate your efforts, and I gave a sincere effort not only to understand your model, but also to think about it, if it makes sense, and if it is feasible and compelling. Does the mere fact that you explained it means, that I would have to swallow it without giving a closer look at your assertions and accept them because you have a P.hD, or because you feel you are a ribosomologist authority? I mean, the mere fact that you spend years reading and studying science papers on the subject, does that mean automatically mean, that your philosophical inferences drawn ( without a shred of empirical evidence to back up your claims ) must be true by default?
If you expected that, then I suppose, you know better by now?!

Dimiter: This translation contains only a few aa and an only a short set of RNAs. Although this claim is not proven directly experimentally, it is supported by numerous experimental data: Yarus, every day PCRs, Arg interactions, Caetano-Anollés model (from 2012) for step by step, loop by loop, helix by helix evolutionary conclusions, and so on.
Reply:  Once again, I do not need to resort to creationist papers and articles, but to your peer, Koonin, which is very honest about the status quo and situation:

Koonin, the logic of chance, page 376
Breaking the evolution of the translation system into incremental steps, each associated with a biologically plausible selective advantage is extremely difficult even within a speculative scheme let alone experimentally. Speaking of ribosomes, they are so well structured that when broken down into their component parts by chemical catalysts (into long molecular fragments and more than fifty different proteins) they reform into a functioning ribosome as soon as the divisive chemical forces have been removed, independent of any enzymes or assembly machinery – and carry on working.  Design some machinery which behaves like this and I personally will build a temple to your name!

Dimiter: It is supported by numerous co-observations that fit the model (look my second paper for example). The peptidyl transfer can occur even without PTC in some conditions and a primitive ribosome can work well enough for simple pre-LUCA forms. PTC center dramatically increases the efficiency and the entire ribosome assembly, but it is NOT an absolute requirement to have peptide synthesis. But no, you of course do not appreciate that. You continue to paste the same argument that if you remove something nothing can work. “…if even one tiny piece is missing, nothing goes. Imagine, you have fully operational translation machinery, and instead of all aminoacyl tRNA synthetases are present, what would happen? The entire translation process would absolutely break down…..” Yes, in your steady imaginary world you are correct, but I give you enough arguments that this MODEL is wrong and the world is NOT steady.
The sad notion is that just because you desperately want your model to be correct, you are IGNORING to acknowledge what the data are for. 
Reply: 
I am sorry, Dimiter, but you have not provided ANY DATA whatsoever to back up your model. It's all just conjecture based on the presupposition that evolution even operates abiotically ( which, funny, tough, even Aron Ra pointed out ) is not true. Darwinian evolution works when life and DNA replication starts. There is PLENTY of scientific literature pointing that out !!

The possible mechanisms to explain the origin of life
https://reasonandscience.catsboard.com/t2515-abiogenesis-the-possible-mechanisms-to-explain-the-origin-of-lif

Dimiter: If you would like to play as a scientist, please follow the scientific way AND do not pick up only the text phrases that suited your view and interpret it wrongly.
I know you are feeling yourself in a mission to distribute the biblical TRUTH.
Reply:  In our interactions, Dimiter, did in NOWHERE cite or propose my religious beliefs for anything. All I infer is that intelligent design is a far better and more case-adequate explanation than unguided evolutionary explanations. The mere fact that you mention this, demonstrates your PREJUDICE AGAINST religion, and in special, our model. Should a scientist not be as unbiased as possible, and PERMIT the scientific evidence to lead wherever it is, EVEN IF it does not fit the preconceived outcome? That's NOT what you seem to do. You seem rather like a veteran evolutionary biologist, which is unable to look outside of your evolutionary thinking, and try to force your ideas and models to others, and feel frustrated, when there is no success.... why is that so?

Dimiter: As the Indian Jones told me: “archeology (understand as science) does not work with the TRUTH, it works with FACTS”. 
Reply:  That's fine in operational science, where the quest is to find out how things factually work in the molecular world. But investigators of history do not have a time machine to travel back in the past and see what happened. So we apply the inference to the best explanation. Which you, unfortunately, have yet to provide, since the glaring gaps that your model still has, are not reasonably filled with materialism.

Dimiter: So to say, science is not about TRUTH, but about FACTS.  Ask yourself: if the Bible is correct and if the science is correct, why those two should contradict? Does not make sense. 
Reply:  Is science correct by default? No. Is the Bible correct by default IF the God of the Bible exists, and if he IS indeed the creator of life, and IF he is truthful? YES.
But that's NOT what I have done all along. I have started from the premise of what is, the evidence seen in the natural world, and FROM THERE, drawn meaningful conclusions. I do not adopt a presupposition in my scientific endeavor and thinking ( despite being a Christian, and, yes, of course, I have a bias as well ), but that is precisely what methodological naturalism forces scientists to do: To FORCE natural explanations, even IF the evidence does not support the explanations.

Historical sciences, and methodological naturalism
https://reasonandscience.catsboard.com/t1692-historical-sciences-and-methodological-naturalism

Possible Emergence of Sequence-Specific RNA Aminoacylation via Peptide Intermediary to Initiate Darwinian Evolution and Code through Origin of Life
Dimiter Kunnev: 2018 Oct 2 1

Observation: An overarching need is to establish interactions between the carrier of genetic information and that of structure/function. It is unclear how the initial relationships between RNA and proteins came to being, bearing in mind that RNA needs proteins to replicate and proteins need RNA to be coded (a problem known as “chicken and egg dilemma”).
Reply: Correct. And how was this established by unguided events? The relationship of information systems directing and controlling the making and operating of machines and factories is ALWAYS tracked back to intelligence.

An organizational structure would have to be established between the domain of information and computation ( the genome ) and the mechanistic domain, where proteins and enzymes work based on the direction and information flow of the beforementioned instructional genetic information. The puzzle lies with the problem of creating a causal organization, the interrelationship of informational and mechanical aspects into interdependent narratives. One of the challenges of life’s origin is thus to explain how instructional information control systems emerge naturally and spontaneously from mere chemical interactions and start taking over the clever making and direction of molecular mechanical dynamics. In modern cells, to make proteins, at least 25 unimaginably complex biosyntheses and production-line like manufacturing steps through large multimolecular machines are required to make proteins. Each step along the way requires exquisitely engineered molecular machines composed of an enormous number of subunits and co-factors. These molecular machines require by their own synthesis through complex multistep assembly processes using many scaffold proteins, co-factors, and chaperones, which orchestrate the biogenesis and assembly of these macromolecular highly complex holoprotein complexes. Machines, making machines, that make machines. How could all this come about by natural means? Incredulity that unguided mechanisms could come with this is justified.  

Paul Davies, the fifth miracle page 53:
Since most large molecules needed for life are produced only by living organisms and are not found outside the cell, how did they come to exist originally, without the help of a meddling scientist? Could we seriously expect a Miller-Urey type of soup to make them all at once, given the hit-and-miss nature of its chemistry?

The four interdependent requirements to have an information transmission system
https://reasonandscience.catsboard.com/t3030-the-four-interdependent-requirements-to-have-an-information-transmission-system
Information is what is conveyed or represented by a particular arrangement or sequence of things. To have an information transmission system, the following things are indispensable, essential, and required ( if any of those is missing, information transmission cannot be established - all have to be precisely defined in advance before any form of communication can be possible at all):

1. A language, 2. the information (message) produced upon that language, 3. an information storage mechanism ( a hard disk, paper, etc.), 4. an information transmission system, that is: encoding - sending and decoding, and eventually fifth ( not essential): 5. translation

Claim: In strong support of the RNA world are the many ribozymes selected under laboratory conditions for almost all the steps of translation.
Reply: No evidence that RNA molecules ever had a broad range of catalytic activities
https://reasonandscience.catsboard.com/t2243-no-evidence-that-rna-molecules-ever-had-the-broad-range-of-catalytic-activities

Another point not considered in this paper is the fact that either in bacteria or the nucleolus in eukaryotic cells, the make of ribosomes is encapsulated in a protected environment through the membrane. The nucleolus is a huge aggregate of macromolecules, including the rRNA genes themselves, precursor rRNAs, mature rRNAs, rRNA-processing enzymes, snoRNPs, a large set of assembly factors (including ATPases, GTPases, protein kinases, and RNA helicases), ribosomal proteins, and partly assembled ribosomes. Those are concentrated and at disposition for the ribosome assembly. The close association of all these components allows the assembly of ribosomes to occur rapidly and smoothly. This environment was not extant on the prebiotic earth unless someone posits that the basic molecules involved in translation were concentrated somehow into a lipid vesicle. How that concentration could have occurred is beyond my imagination nor understanding, and considerable skepticism that it is feasible is in my view justified.

Dimiter: Hello, look carefully, where did you see “no homologous sequence of the eukaryotic and prokaryotic ribosome”. Your interpretation of the claim in the paper is in your way, but it not what the authors say. There is sequence homology in some more and some less and this is normal to explain from the evolutionary model. But let’s go to a more fundamental problem: THE MODEL
Reply: Ok. But there ARE particles that are not homologous, like the 5.8S RNA which is unique to eukaryotes

Eukaryotic Protein Synthesis Differs from Prokaryotic Protein Synthesis Primarily in Translation Initiation
https://www.ncbi.nlm.nih.gov/books/NBK22531/

Questioning that so many differences could be explained by evolutionary means is more than justified.

Another point in question: If there were an evolutionary transition from a more simple prokaryotic ribosome, to a more complex ribosome in eukaryotes, not only the evolution and transition from a simpler to a more complex ribosome would have to be explained, but also the origin of the nucleolus and eventual possible evolution of orchestration of import of the two ribosomal subunits which attain their final functional form only after each is individually transported through the nuclear pores into the cytoplasm. Other ribonucleoprotein complexes, including telomerase, are also assembled in the nucleolus.

My comment: How was this transport programmed and orchestrated? By unguided, nonintelligent processes? Trial and error? How likely and feasible is that? 



All information storage devices, code languages, blueprints, information transmission systems, translation ciphers, with the purpose to make factories, and interdependent factory parks made upon those instructions are of intelligent origin. The Ribosome signaling networks are therefore the result of Intelligent design.

This machinery is consistent with the idea that positioning of the reactive groups is the critical factor for catalysis, but does not exclude assistance from ribosomal or substrate moieties. Hence, by offering the frame for correct substrate positioning, as well as for catalytic contribution of the P-site tRNA 2′-hydroxyl group, it became evident that the ribosomal architectural frame governs the positional requirements and provides the means for substrate-mediated chemical catalysis.

Observation:  Any architectural conformation that is not precisely as the fully developed one will by non-functional. A stepwise evolutionary emergence is therefore not feasible. Architecting a precise functional position requires foresight and engineering skills which only intelligent agents are capable of.

The transition state for formation of the peptide bond in the ribosome
https://www.pnas.org/content/103/36/13327

 50 atoms are important in the peptide formation mechanism.  This ribosomal elaborate architectural design guides the process of peptide-bond reaction by forcing a rotational motion consistent with the 2-fold rotation axis.  In all respects, it makes good chemical sense, in terms of formation of a peptide bond, the translocation of A-site tRNA to the P site, and P-site tRNA separation from the elongated chain. The chemical sense, after the mathematical criteria, is what corroborates the TS.  The TS is characterized mathematically by normal mode frequencies that are all positive, except for exactly one, which is negative and corresponds to a vibration along the reaction coordinate sending the old reactants into the new products.

Observation:  Even if the claim is that just 50 atoms would be important for the peptide formation mechanism, the odds to have that conformation by random chance would be fare beyond what random shuffling in this vast sequence space would be capable of achieving.

https://www.nature.com/collections/gjbhcpwgss
Understanding how the simple molecules present on the early Earth may have given rise to the complex systems and processes of contemporary biology is widely regarded as one of chemistry's great unsolved questions

Quantum mechanic glimpse into peptide bond formation within the ribosome shed light on origin of life
https://link.springer.com/article/10.1007/s11224-017-0980-5

The structure of the Peptidyl Transferase Center pocket  seems to be ingeniously built for accommodating the 3′ ends of the A- and P-site tRNAs

The preservation of RNA activity in performing the extremely important process of genetic code translation indicates that RNA is capable of handling the complexity of the current cellular life, which requires a highly controlled sophisticated regulatory mechanism. Obviously, translation is much more complicated than accidental peptide bond formation. 

Remarkably, within the contemporary ribosomes, the distances between the regions involved in the ribosome’s function are far beyond the possibility of any direct Bchemical talk^ (70–140 A). The symmetrical region is located at the heart of the ribosome and chemically connects to all of the ribosome functional centers involved in translation. Hence, it can transmit signals between them. 

Observation: Signaling means communication. 

The four interdependent requirements to have an information transmission system
https://reasonandscience.catsboard.com/t3030-the-four-interdependent-requirements-to-have-an-information-transmission-system

Information is what is conveyed or represented by a particular arrangement or sequence of things. To have an information transmission system, the following things are indispensable, essential, and required ( if any of those is missing, information transmission cannot be established - all have to be precisely defined in advance before any form of communication can be possible at all):  1. A language2. the information (message) produced upon that language,  the 3 .information storage mechanism ( a hard disk, paper, etc.), 4. an information transmission system, that is: encoding - sending and decoding) and eventually fifth ( not essential): 5. translation. 

All information storage devices, code languages, blueprints, information transmission systems, translation ciphers, with the purpose to make factories, and interdependent factory parks made upon those instructions are of intelligent origin. The Ribosome signaling networks are therefore the result of Intelligent design.

This machinery is consistent with the idea that positioning of the reactive groups is the critical factor for catalysis, but does not exclude assistance from ribosomal or substrate moieties. Hence, by offering the frame for correct substrate positioning, as well as for catalytic contribution of the P-site tRNA 2′-hydroxyl group, it became evident that the ribosomal architectural frame governs the positional requirements and provides the means for substrate-mediated chemical catalysis.

Observation:  Any architectural conformation that is not precisely as the fully developed one will by non-functional. A stepwise evolutionary emergence is therefore not feasible. Architecting a precise functional position requires foresight and engineering skills which only intelligent agents are capable of.

The transition state for formation of the peptide bond in the ribosome
https://www.pnas.org/content/103/36/13327

 50 atoms are important in the peptide formation mechanism.  This ribosomal elaborate architectural design guides the process of peptide-bond reaction by forcing a rotational motion consistent with the 2-fold rotation axis.  In all respects, it makes good chemical sense, in terms of formation of a peptide bond, the translocation of A-site tRNA to the P site, and P-site tRNA separation from the elongated chain. The chemical sense, after the mathematical criteria, is what corroborates the TS.  The TS is characterized mathematically by normal mode frequencies that are all positive, except for exactly one, which is negative, and corresponds to a vibration along the reaction coordinate sending the old reactants into the new products.  

On origin of life
The high conservation of the proto-ribosome nucleotide sequence is suggestive of its robustness under diverse environmental conditions and hence hints at its prebiotic origin.
My comment: It is also evidence that a gradual, evolutionary, step-wise evolution of the sequence would be non-functional, and indication, that the Ribosome had to emerge from the start, fully functional and operational, "as is".

The A andP sites are close enough together for their two tRNA molecules to be forced to form base pairs with adjacent codons on the mRNA molecule. This feature of the ribosome maintains the correct reading frame on the mRNA.
Comment: that means, in order to maintain the correct reading frame on the mRNA, the configuration of the A and P sites to be close enough together IS VITAL. How could this configuration have emerged randomly? Trial and error? This tiny fact means, there is no tolerance here. It is an all or nothing business. The configuration HAS TO BE RIGHT just from the beginning. A down up development to get the right distance will be always non-functional. Another important evidence that demonstrates that evolutionary means are not adequate to explain the feat in question.  

On origin of life
The high conservation of the proto-ribosome nucleotide sequence is suggestive of its robustness under diverse environmental conditions and hence hints at its prebiotic origin.
My comment: It is also evidence that a gradual, evolutionary, step-wise evolution of the sequence would be non-functional, and indication, that the Ribosome had to emerge from the start, fully functional and operational, "as is".


The Ribosome is one of the greatest wonders of molecular nanotechnology ever devised by our amazing unfathomable creator.
Koonin, the logic of chance, page 376
Breaking the evolution of the translation system into incremental steps, each associated with a biologically plausible selective advantage is extremely difficult even within a speculative scheme let alone experimentally. Speaking of ribosomes, they are so well structured that when broken down into their component parts by chemical catalysts (into long molecular fragments and more than fifty different proteins) they reform into a functioning ribosome as soon as the divisive chemical forces have been removed, independent of any enzymes or assembly machinery – and carry on working.  Design some machinery which behaves like this and I personally will build a temple to your name!
My comment: Fortunately, people that recognize the magnificence of the creator of the Ribosome, build him churches and temples all over the globe, and give HIM glory.

Molecular biology of the Cell, Alberts, 6th ed. pg. 369
Producing an overall speed of translation of 20 amino acids incorporated per second in bacteria. Mutant bacteria with a specific alteration in the small ribosomal subunit have longer delays and translate mRNA into protein with an accuracy considerably higher than this; however, protein synthesis is so slow in these mutants that the bacteria are barely able to survive.

Question: How could the right speed have been obtained with trial and error, if slow mutants do not survive? Had the speed not to be right from the beginning?

Recognition of Cognate Transfer RNA by the 30S Ribosomal Subunit
https://sci-hub.st/https://science.sciencemag.org/content/292/5518/897

The ribosome recognizes the geometry of codon anticodon base pairing in a way that would discriminate against near-cognate tRNAs. The minor groove of the first and second base pairs between the codon and anticodon is closely monitored by a set of interactions that are induced by the binding of cognate tRNA. These interactions would be disrupted by mismatches, so that the induced structural changes would no longer be energetically favorable. The third or “wobble” position has less stringent constraints, and therefore can allow a broader range of base-pairing geometries, consistent with the requirements of the genetic code. 

My comment: Monitoring and taking action when something is wrong requires "knowledge" of the correct state, "knowledge" of the wrong state, and know how to correct the wrong state. Knowledge, monitoring, error recognition and repair are actions only known to be performed by intelligence. 

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316189/



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33Translation through ribosomes,  amazing nano machines - Page 2 Empty Imprints of the genetic code in the ribosome on Sat Oct 03, 2020 12:57 pm

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Imprints of the genetic code in the ribosome
https://www.pnas.org/content/107/18/8298.full

The establishment of the genetic code remains elusive nearly five decades after the code was elucidated. The stereo chemical hypothesis postulates that the code developed from interactions between nucleotides and amino acids, yet supporting evidence in a biological context is lacking. We show here that anticodons are selectively enriched near their respective amino acids in the ribosome, and that such enrichment is significantly correlated with the canonical code over random codes.

Although multiple hypotheses have been proposed to explain why codons are selectively assigned to specific amino acids, empirical data are extremely rare and difficult to obtain leaving many theories in the realm of conjecture. Our results suggest that the essence of the primitive RNA-amino acid interaction remains at the heart of modern ribosomes

The Ribosome: Perfectionist Protein-Maker Trashes Error

http://reasonandscience.heavenforum.org/t1661-ribosomes-amazing-nano-machines


http://iaincarstairs.wordpress.com/2013/03/25/as-smart-as-molecules/

One machine common to all life on Earth is the ribosome.  Its strongly conserved nature, and the common sense observation that it makes everything else, indicates its central position in evolution.  The ribosome is not a single tool but a workshop split into two major parts, all created (using E. coli as an example) from around 7,400 amino acids, and around 250,000 atoms, all primed to use the strongest possible codon-amino acid mapping out of a practically endless range of possibilities.

Ribosomes can be so numerous as to make up 25% of the cell mass of E. coli. A striking feature of the ribosome is that, even given the large assorted collection of subunits, it self-assembles in vitro!

The core of the ribosome is RNA, supporting the idea that early forms of life relied on RNA rather than DNA.  But if such a workshop is necessary to create proteins, whether from templates of RNA or DNA – from where could the ribosome come from?  More vexing still for Darwinism is how editorial precision could arise in a system in which errors themselves were the key to prolific reproductive success at the start.  Why change a winning hand?

New discoveries are being made about the ribosome all the time.  Relevant to Darwinism, in 2009 Nature published some new discoveries by Johns Hopkins researchers concerning the remarkable actions of the ribosome’s ruthless quality control editor; if you think I tend to anthropomorphise molecules, note how the researchers detail -

   ..a new “proofreading step” during which the suite of translational tools called the ribosome recognizes errors, just after making them, and definitively responds by hitting its version of a “delete” button.

   It turns out.. ..that the ribosome exerts far tighter quality control than anyone ever suspected over its precious protein products which, as workhorses of the cell, carry out the very business of life.

   “What we now know is that in the event of miscoding, the ribosome cuts the bond and aborts the protein-in-progress, end of story,” says Rachel Green, a Howard Hughes Medical Institute investigator and professor of molecular biology and genetics in the Johns Hopkins University School of Medicine. “There’s no second chance.”

   “We thought that once the mistake was made, it would have just gone on to make the next bond and the next,” Green says. “But instead, we noticed that one mistake on the ribosomal assembly line begets another, and it’s this compounding of errors that leads to the partially finished protein being tossed into the cellular trash.”

   To their further surprise, the ribosome lets go of error-laden proteins 10,000 times faster than it would normally release error-free proteins, a rate of destruction Green says is “shocking” and reveals just how much of a stickler the ribosome is about high-fidelity protein synthesis.

   http://phys.org/news150559493.html#jCp




The translation process in the ribosome to occur, the ribosome must be able to proceed and go through the full translation sequence, it must be fully functional, no intermediate evolutionary stage will do it : beside this, it consists of two main subunits, ( beside a significant number of co-factors , which help in the build up process of the ribosome ) which makes it a irreducible complex system.

Replication most probably would not occur at pre-stage of a common ancestor, so evolution cannot be proposed as a driving factor at this stage.

lifeorigin::
RNA replication in the lab makes use of extensive investigator interference. Chemicals like amino acids, aldehydes, and sugars (other than ribose) are arbitrarily excluded. Very specific activation agents are used to encourage replication (ImpA for adenine, ImpG for guanine, ImpC for cytosine, and ImpU for uracil). The concentration of the chemicals (especially cytosine and ribose) is billions and billions of orders of magnitude higher than what one would expect under plausible prebiotic conditions.

Shajani Z :
Ribosome assembly needs the contributions of several assembly cofactors , including Era, RbfA, RimJ, RimM, RimP, and RsgA, which associate with the 30S subunit, and CsdA, DbpA, Der, and SrmB, which associate with the 50S subunit. These subunits would have no function of their own, why then would random processes produce them without a final goal and no forsight of function ?
Five following conditions would all have to be met in the biosynthesis process of the Ribosome:
Kairosfocus
C1: Availability. Among the parts available for recruitment to form a biological system consisting of multiple parts, there would need to be ones capable of performing the highly specialized tasks of the specific system, even though all of the items serve some other function or no function in another system where they were recruited from.
C2: Synchronization. The availability of these parts would have to be synchronized so that at some point, either individually or in combination, they are all available at the same time.
C3: Localization. The selected parts must all be made available at the same ‘construction site,’ perhaps not simultaneously but certainly at the time they are needed.
C4: Coordination.The parts must be mutually compatible, that is, ‘well-matched’ and capable of properly ‘interacting’: even if the subunits  are put together in the right order, they also need to interface correctly.

The parts must be coordinated in just the right way: even if all of the parts of a ribosome are available at the right time, it is clear that the majority of ways of assembling them will be non-functional or irrelevant.
C5: Interface compatibility. The parts must be mutually compatible, that is, ‘well-matched’ and capable of properly ‘interacting’: even if the subunits are put together in the right order, they also need to interface correctly.

Resumed : For the assembly of a biological system of multiple parts, following steps must be explained : the origin of the genome information to produce all subunits and assembly cofactors. Parts availability, synchronization, manufacturing and assembly coordination through genetic information, and interface compatibility. The individual parts must precisely fit together. All these steps are better explained through a super intelligent and powerful designer, rather than mindless natural processes by chance, or /  and evolution,  since we observe all the time minds capabilities producing  machines and factories, producing machines and end products.



http://www.hopkinsmedicine.org/news/media/releases/Lost_In_Translation

The enzyme machine that translates a cell's DNA code into the proteins of life is nothing if not an editorial perfectionist

Johns Hopkins researchers, reporting in the journal Nature January 7, have discovered a new "proofreading step" during which the suite of translational tools called the ribosome recognizes errors, just after making them, and definitively responds by hitting its version of a "delete" button.

It turns out, the Johns Hopkins researchers say, that the ribosome exerts far tighter quality control than anyone ever suspected over its precious protein products which, as workhorses of the cell, carry out the very business of life.

and it's this compounding of errors that leads to the partially finished protein being tossed into the cellular trash," she adds.

To their further surprise, the ribosome lets go of error-laden proteins 10,000 times faster than it would normally release error-free proteins, a rate of destruction that Green says is "shocking" and reveals just how much of a stickler the ribosome is about high-fidelity protein synthesis. "The cell is a wasteful system in that it makes something and then says, forget it, throw it out,"

That looks all ingeniously designed.......

http://www.nytimes.com/2009/10/08/science/08nobel.html?_r=0
Besides the implications for biomedical research, another consequence of the ribosome work was to resolve an old “classic chicken and egg problem” , Dr. Berg of the National Institute of General Medical Sciences explained. If ribosomes are needed to make proteins but they are also made of proteins, which came first?

J.Sarfati :
the DNA information requires a complex decoding machine, the ribosome, but the instructions to build ribosomes are on the DNA. And decoding requires energy from ATP, built by ATP-synthase motors, built from instructions in the DNA decoded by ribosomes … “vicious circles” for any materialistic origin theory, as leading philosopher of science Karl Popper put it .

http://newswire.rockefeller.edu/2013/08/14/structural-biologist-interested-in-ribosome-assembly-to-join-rockefeller-faculty/
What’s more, it’s something of a chicken-and-egg problem. “You need the machinery to be in place in order to manufacture proteins, but the machinery itself is made of proteins that must be manufactured,” Klinge says.

well, as far as i know without ribosomes there is no protein synthesis, without protein synthesis there is no life, without life there is no evolution so ribosomes cant come to existence via evolution so how did the form?

Facing these facts, i believe theists are justified to hold the position, that design explains best the origin of Ribosomes, and the origin of life.

[/quote]


well, as far as i know without ribosomes there is no protein synthesis, without protein synthesis there is no life, without life there is no evolution so ribosomes cant come to existence via evolution so how did the form?

The translation process in the ribosome to occur, the ribosome must be able to proceed and go through the full translation sequence, it must be fully functional, no intermediate evolutionary stage will do it : beside this, it consists of two main subunits, ( beside a significant number of co-factors , which help in the build up process of the ribosome ) which makes it a irreducible complex system.

Replication most probably would not occur at pre-stage of a common ancestor, so evolution cannot be proposed as a driving factor at this stage.

lifeorigin::
RNA replication in the lab makes use of extensive investigator interference. Chemicals like amino acids, aldehydes, and sugars (other than ribose) are arbitrarily excluded. Very specific activation agents are used to encourage replication (ImpA for adenine, ImpG for guanine, ImpC for cytosine, and ImpU for uracil). The concentration of the chemicals (especially cytosine and ribose) is billions and billions of orders of magnitude higher than what one would expect under plausible prebiotic conditions.

Shajani Z :Ribosome assembly needs the contributions of several assembly cofactors , including Era, RbfA, RimJ, RimM, RimP, and RsgA, which associate with the 30S subunit, and CsdA, DbpA, Der, and SrmB, which associate with the 50S subunit. These subunits would have no function of their own, why then would random processes produce them without a final goal and no forsight of function ?

Five following conditions would all have to be met:
Kairosfocus
C1: Availability. Among the parts available for recruitment to form the flagellum, there would need to be ones capable of performing the highly specialized tasks of paddle, rotor, and motor, even though all of these items serve some other function or no function.
C2: Synchronization. The availability of these parts would have to be synchronized so that at some point, either individually or in combination, they are all available at the same time.
C3: Localization. The selected parts must all be made available at the same ‘construction site,’ perhaps not simultaneously but certainly at the time they are needed.
C4: Coordination.
Besides the implications for biomedical research, another consequence of the ribosome work was to resolve an old “classic chicken and egg problem” about evolution,
J.Sarfati :
the DNA information requires a complex decoding machine, the ribosome, but the instructions to build ribosomes are on the DNA. And decoding requires energy from ATP, built by ATP-synthase motors, built from instructions in the DNA decoded by ribosomes … “vicious circles” for any materialistic origin theory, as leading philosopher of science Karl Popper put it .

http://newswire.rockefeller.edu/2013/08/14/structural-biologist-interested-in-ribosome-assembly-to-join-rockefeller-faculty/
What’s more, it’s something of a chicken-and-egg problem. “You need the machinery to be in place in order to manufacture proteins, but the machinery itself is made of proteins that must be manufactured,” Klinge says.

Shajani Z : :A ribosome consists of 50–70 different components and is, therefore, one of the most complicated structures known in biology. The large number of components requires a highly coordinated synthesis and assembly.

The parts must be coordinated in just the right way: even if all of the parts of a ribosome are available at the right time, it is clear that the majority of ways of assembling them will be non-functional or irrelevant.
C5: Interface compatibility. The parts must be mutually compatible, that is, ‘well-matched’ and capable of properly ‘interacting’: even if the subunits  are put together in the right order, they also need to interface correctly.

Resumed : For the assembly of a Ribosome, following steps must be explained : the origin of the genome information to produce all Ribosome subunits and assembly cofactors. Parts availability, synchronization, manufacturing and assembly coordination through genetic information, and interface compatibility. The individual parts must precisely fit together. All these steps are better explained through a super intelligent and powerful designer, rather than mindless natural processes by chance, or /  and evolution,  since we observe all the time minds capabilities producing ribosome-like machines and factories, producing machines and end products.


http://www.ncbi.nlm.nih.gov/pubmed/21529161
Shajani Z :
A ribosome consists of 50–70 different components and is, therefore, one of the most complicated structures known in biology. The large number of components requires a highly coordinated synthesis and assembly.


http://www.nobelprize.org/educational/medicine/dna/a/translation/ribosome_ass.html

This example of the Rate of Ribosome Synthesis is quite startling:

*HeLa cells (a type of human tumour cells) divide each 24 hours.
* Each cell contains around 10 million ribosomes, i.e. 7000 ribosomes are produced in the nucleolus each minute.
*Each ribosome contains around 80 proteins, i.e. more than 0.5 million ribosomal proteins are synthesised in the cytoplasm per minute.
*The nuclear membrane contains approximately 5000 pores. Thus, more than 100 ribosomal proteins are imported from the cytoplasm to the nucleus per pore and minute. At the same time 3 ribosomal subunits are exported from the nucleus to the cytoplasm per pore and minute.




http://sws1.bu.edu/mfk/ribosome.pdf

Translation through ribosomes,  amazing nano machines - Page 2 Whatrecentribosomestructureshaverevealedaboutthemechanismoftranslation-ribosomepdf2014-04-1212-17-49_zps2906deaf


Althougheven this basic pathway is very complicated, translation involves many other features that have also been the subject of structural and functional studies in recent years. These include the rescue of stalled ribosomes, programmed frameshifting, the interaction of the nascent peptide with the exit tunnel, the modification of the peptide as it emerges from the ribosome, its folding and its transport across or insertion into membranes, and the regulation of translation. the extremely complicated field of eukaryotic translation, especially initiation, is sure to be increasingly targeted by biophysical and biochemical techniques.

Overview of bacterial translation. For simplicity, not all intermediate steps are shown. The colour scheme shown here is used consistently throughout this review. aa-tRNA, aminoacyl-tRNA; EF elongation factor; IF, initiation factor; RF, release factor.


Ribosomes composed of two subunits

3d:
http://www.rcsb.org/pdb/explore/jmol.do?structureId=2WDK&split=yes&asymIds=2WDK%2C2WDL%2C2WDM%2C2WDN&bionumber=1

A Ribosome is composed of two subunits, made of RNA chains with proteins bound on the outside.  The molecular movements of this complex provides a specific catalyst for the creation of amino-acid polymers.   These biological nanomachines are the 3D printers of the cell, producing thousands of different proteins.

http://cellmorphs.tumblr.com/

A Ribosome is composed of two subunits, made RNA chains and proteins bound on its outside.  The molecular movements of this complex provide a very specific catalyst for the creation of amino-acid polymers.   These biological nanomachines are the 3D printers of the cell, producing thousands of different proteins.

Ahh, the mighty ribosome. A biological machine comprised of an elaborate conglomeration of intricately-folded proteins and RNAs, none capable of building anything on its own, but together creating nature’s most advanced piece of chemical machinery.

It’s a fascinating chicken-and-egg problem written in nucleic and amino acids, a thing that has to exist in order to make itself


It’s also a thing that has to exist to make any of us, the translator of the genetic code, taking the instructions for life and assembling the things that do stuff inside of all of life.

When I look at this, I see the incredible beauty of evolution Gods creation  written in chemistry.

http://cshperspectives.cshlp.org/content/4/4/a003681.full
The molecular evolution of translation poses at least three difficult questions: (1) The chicken-or-the-egg problem: if the ribosome requires proteins to function, where did the proteins come from to make the first ribosome? (2) What was the driving force for evolution of the ribosome? and (3) How did coding arise? Thanks to numerous advances in this field, we now have a likely answer to the first question and a plausible basis for answering the second. Despite many decades of thinking about the third question, the origins of coding remain a puzzle. Another question, implicit in the RNA World hypothesis, is (4) Can we account for...

Leading Biologists Marvel at the "Irreducible Complexity" of the Ribosome, but Prefer Evolution-of-the-Gaps

Professor of Genetics at Harvard Medical School and Director of the Center for Computational Genetics, similarly marveled at the complexity of the ribosome:

The ribosome, both looking at the past and at the future, is a very significant structure,  it's the most complicated thing that is present in all organisms.It can change from DNA three nucleotides into one amino acid. That's really marvelous. We need to understand that better.

Craig Venter suggested that by sequencing the genomes of more organisms perhaps we could reconstruct a primitive precursor ribosome. But Church is skeptical that this is unlikely to help because current biology reveals that a minimum number of genes are required for a functional ribosome--and that minimum number is still quite large:

But isn't it the case that, if we take all the life forms we have so far, isn't the minimum for the ribosome about 53 proteins and 3 polynucleotides? And hasn't that kind of already reached a plateau where adding more genomes doesn't reduce that number of proteins?

The conversation that follows is striking, showing that as far as we know, the ribosome has "irreducibly complexity":


   VENTER: Below ribosomes, yes: you certainly can't get below that. But you have to have self-replication.

   CHURCH: But that's what we need to do -- otherwise they'll call it irreducible complexity. If you say you can't get below a ribosome, we're in trouble, right? We have to find a ribosome that can do its trick with less than 53 proteins.

   VENTER: In the RNA world, you didn't need ribosomes.

   CHURCH: But we need to construct that. Nobody has constructed a ribosome that works well without proteins.

   VENTER: Yes.

   SHAPIRO: I can only suggest that a ribosome forming spontaneously has about the same probability as an eye forming spontaneously.

   CHURCH: It won't form spontaneously; we'll do it bit by bit.

   SHAPIRO: Both are obviously products of long evolution of preexisting life through the process of trial and error.

   CHURCH: But none of us has recreated that any.

   SHAPIRO: There must have been much more primitive ways of putting together

   CHURCH: But prove it.

We don't know how the ribosome and its required proteins evolved, but we know that "Both are obviously products of long evolution of preexisting life through the process of trial and error." This is a prime example of "evolution-of-the-gaps,"



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34Translation through ribosomes,  amazing nano machines - Page 2 Empty CNC Machining and One Ruthless Editor on Sat Oct 03, 2020 3:42 pm

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CNC Machining and One Ruthless Editor

The ribosome is not a single tool but a workshop split into two major parts, all created  from around 7,400 amino acids ( E. coli ), and around 250,000 atoms, all primed to use the strongest possible codon-amino acid mapping out of a practically endless range of possibilities.

Ribosomes can be so numerous as to make up 25% of the cell mass of E. coli. A striking feature of the ribosome is that, even given the large assorted collection of subunits, it self-assembles in vitro!

The core of the ribosome is RNA, supporting the idea that early forms of life relied on RNA rather than DNA.  But if such a workshop is necessary to create proteins, whether from templates of RNA or DNA – from where could the ribosome come from?  More vexing still for Darwinism is how editorial precision could arise in a system in which errors themselves were the key to prolific reproductive success at the start.  Why change a winning hand?

New discoveries are being made about the ribosome all the time.  In 2009 Nature published some new discoveries by Johns Hopkins researchers concerning the remarkable actions of the ribosome’s ruthless quality control editor; if you think I tend to anthropomorphise molecules, note how the researchers detail -

..a new “proofreading step” during which the suite of translational tools called the ribosome recognizes errors, just after making them, and definitively responds by hitting its version of a “delete” button.

It turns out.. ..that the ribosome exerts far tighter quality control than anyone ever suspected over its precious protein products which, as workhorses of the cell, carry out the very business of life.

“What we now know is that in the event of miscoding, the ribosome cuts the bond and aborts the protein-in-progress, end of story,” says Rachel Green, a Howard Hughes Medical Institute investigator and professor of molecular biology and genetics in the Johns Hopkins University School of Medicine. “There’s no second chance.”

“We thought that once the mistake was made, it would have just gone on to make the next bond and the next,” Green says. “But instead, we noticed that one mistake on the ribosomal assembly line begets another, and it’s this compounding of errors that leads to the partially finished protein being tossed into the cellular trash.”

To their further surprise, the ribosome lets go of error-laden proteins 10,000 times faster than it would normally release error-free proteins, a rate of destruction Green says is “shocking” and reveals just how much of a stickler the ribosome is about high-fidelity protein synthesis.

https://web.archive.org/web/20130503211721/http://iaincarstairs.wordpress.com/2013/03/25/as-smart-as-molecules/

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35Translation through ribosomes,  amazing nano machines - Page 2 Empty Ribosome of escheria coli: on Sat Oct 03, 2020 3:43 pm

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Ribosome of escheria coli:

In eubacteria and archaea the large subunit comprises ~3,000 nucleotides of ribosomal RNA (rRNA), > 30 proteins and sediments at 50S, whereas the ~1,500 nucleotides and > 20 proteins of the smaller subunit sediment at 30S. These conveniently different sedimentation coefficients are used as descriptors of the large (50S) and the small (30S) ribosomal subunits, while the entire ribosomal particle is referred to as the 70S ribosome (in eukaryotes these are 60S, 40S and 80S, respectively).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783306/

Subunit composition of ribosome 
[(RrsA)(RpsA)(RpsB)(RpsC)(RpsD)(RpsE)(RpsF)(RpsG)(RpsH)(RpsI)(RpsJ)(RpsK)(RpsL)(RpsM)(RpsN)(RpsO)(RpsP)(RpsQ)(RpsR)(RpsS)(RpsT)(RpsU)(Sra)][(RrlA)(RrfA)(RplA)(RplB)(RplC)(RplD)(RplE)(RplF)([RplJ][(RplL)2]2)(RplI)(RplK)(RplM)(RplN)(RplO)(RplP)(RplQ)(RplR)(RplS)(RplT)(RplU)(RplV)(RplW)(RplX)(RplY)(RpmA)(RpmB)(RpmC)(RpmD)(RpmE)(RpmF)(RpmG)(RpmH)(RpmI)(RpmJ)]

30S ribosomal subunit 
(RrsA)(RpsA)(RpsB)(RpsC)(RpsD)(RpsE)(RpsF)(RpsG)(RpsH)(RpsI)(RpsJ)(RpsK)(RpsL)(RpsM)(RpsN)(RpsO)(RpsP)(RpsQ)(RpsR)(RpsS)(RpsT)(RpsU)(Sra) (summary available)
16S ribosomal RNA = RrsA (extended summary available)
30S ribosomal subunit protein S1 = RpsA (extended summary available)
30S ribosomal subunit protein S2 = RpsB (summary available)
30S ribosomal subunit protein S3 = RpsC (summary available)
30S ribosomal subunit protein S4 = RpsD (extended summary available)
30S ribosomal subunit protein S5 = RpsE (extended summary available)
30S ribosomal subunit protein S6 = RpsF (extended summary available)
30S ribosomal subunit protein S7 = RpsG (extended summary available)
30S ribosomal subunit protein S8 = RpsH (extended summary available)
30S ribosomal subunit protein S9 = RpsI (extended summary available)
30S ribosomal subunit protein S10 = RpsJ (extended summary available)
30S ribosomal subunit protein S11 = RpsK (extended summary available)
30S ribosomal subunit protein S12 = RpsL (extended summary available)
30S ribosomal subunit protein S13 = RpsM (extended summary available)
30S ribosomal subunit protein S14 = RpsN (summary available)
30S ribosomal subunit protein S15 = RpsO (extended summary available)
30S ribosomal subunit protein S16 = RpsP (extended summary available)
30S ribosomal subunit protein S17 = RpsQ (summary available)
30S ribosomal subunit protein S18 = RpsR (extended summary available)
30S ribosomal subunit protein S19 = RpsS (summary available)
30S ribosomal subunit protein S20 = RpsT (extended summary available)
30S ribosomal subunit protein S21 = RpsU (summary available)
30S ribosomal subunit protein S22 = Sra (summary available)

50S ribosomal subunit = 
(RrlA)(RrfA)(RplA)(RplB)(RplC)(RplD)(RplE)(RplF)([RplJ][(RplL)2]2)(RplI)(RplK)(RplM)(RplN)(RplO)(RplP)(RplQ)(RplR)(RplS)(RplT)(RplU)(RplV)(RplW)(RplX)(RplY)(RpmA)(RpmB)(RpmC)(RpmD)(RpmE)(RpmF)(RpmG)(RpmH)(RpmI)(RpmJ)
23S ribosomal RNA = RrlA (extended summary available)
5S ribosomal RNA = RrfA (extended summary available)
50S ribosomal subunit protein L1 = RplA (extended summary available)
50S ribosomal subunit protein L2 = RplB (summary available)
50S ribosomal subunit protein L3 = RplC (summary available)
50S ribosomal subunit protein L4 = RplD (extended summary available)
50S ribosomal subunit protein L5 = RplE (extended summary available)
50S ribosomal subunit protein L6 = RplF (extended summary available)
50S ribosomal protein complex L8 = (RplJ)([RplL]2)2 (summary available)
50S ribosomal subunit protein L10 = RplJ (extended summary available)
50S ribosomal subunit protein L7/L12 dimer = (RplL)2
50S ribosomal subunit protein L12 = RplL
50S ribosomal subunit protein L9 = RplI (extended summary available)
50S ribosomal subunit protein L11 = RplK (extended summary available)
50S ribosomal subunit protein L13 = RplM (extended summary available)
50S ribosomal subunit protein L14 = RplN (extended summary available)
50S ribosomal subunit protein L15 = RplO (summary available)
50S ribosomal subunit protein L16 = RplP (extended summary available)
50S ribosomal subunit protein L17 = RplQ (summary available)
50S ribosomal subunit protein L18 = RplR (extended summary available)
50S ribosomal subunit protein L19 = RplS (extended summary available)
50S ribosomal subunit protein L20 = RplT (extended summary available)
50S ribosomal subunit protein L21 = RplU (summary available)
50S ribosomal subunit protein L22 = RplV (extended summary available)
50S ribosomal subunit protein L23 = RplW (extended summary available)
50S ribosomal subunit protein L24 = RplX (extended summary available)
50S ribosomal subunit protein L25 = RplY (extended summary available)
50S ribosomal subunit protein L27 = RpmA (extended summary available)
50S ribosomal subunit protein L28 = RpmB (summary available)
50S ribosomal subunit protein L29 = RpmC (summary available)
50S ribosomal subunit protein L30 = RpmD (summary available)
50S ribosomal subunit protein L31 = RpmE (extended summary available)
50S ribosomal subunit protein L32 = RpmF (summary available)
50S ribosomal subunit protein L33 = RpmG (extended summary available)
50S ribosomal subunit protein L34 = RpmH (extended summary available)
50S ribosomal subunit protein L35 = RpmI (summary available)
50S ribosomal subunit protein L36 = RpmJ (extended summary available)

Initial work in the bacterium Escherichia coli identified the ribosome-interacting protein elongation factor P to be essential for resolving translation stalling at proline stretches. In eukaryotes, the homologous factor eIF5A is a highly abundant35 and essential protein that is comprised of only 157 amino acids and contains a unique post-translational modification called hypusine [G].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054806/



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16S ribosomal RNA 

It has several functions:
Like the large (23S) ribosomal RNA, it has a structural role, acting as a scaffold defining the positions of the ribosomal proteins.
The 3′-end contains the anti-Shine-Dalgarno sequence, which binds upstream to the AUG start codon on the mRNA. The 3′-end of 16S RNA binds to the proteins S1 and S21 known to be involved in initiation of protein synthesis[5]
Interacts with 23S, aiding in the binding of the two ribosomal subunits (50S and 30S)
Stabilizes correct codon-anticodon pairing in the A-site, via a hydrogen bond formation between the N1 atom of adenine residues 1492 and 1493 and the 2′OH group of the mRNA backbone

First, 16S rRNA is present in all known prokaryotic organisms. Second, it is poorly subjected to lateral gene transfer. Third, the extremely conserved scaffolding by ribosomal proteins makes its sequence extremely conserved in certain regions, while other regions not directly involved in the stabilization and exposed to solvent are relatively free from evolutionary constraints, so they were extremely variable . In total, we can count nine variable regions (V1 to V9) of different size in the approximately 1500 bp constituting a full 16S rRNA molecule. Targeting all or some of these regions has been considered in the last two decades the gold standard for phylogenetic studies of microbial communities, as well as for assigning taxonomic names to prokaryotes, both archaea and bacteria.

Translation through ribosomes,  amazing nano machines - Page 2 Riboso25
Perspectives on prokaryote’s ribosome.
(A) Two opposite sides of the 3D structure of the prokaryotic ribosome with ribosomal proteins, 23S rRNA, 16S rRNA and 5S rRNA in white, green, red and blue, respectively.
(B) Two opposite sides of the 3D structure of the prokaryotic ribosome small subunit (SSU) with ribosomal proteins and 16S rRNA in white and red, respectively.
(C) Localization and color-coding of the nine 16S variable regions in the 3D structure of a scaffolded 16S rRNA devoid of ribosomal proteins. 
(D) Localization of the nine, color-coded as in C, 16S variable regions in the classical two-dimensional representation of the 16S rRNA secondary structure from E. coli.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288201/
Translation through ribosomes,  amazing nano machines - Page 2 1024px-16S.svg

16S rRNA secondary structure, showing conserved parts for Prokaryotes (IUPAC letters) and amongst Archea/Bacteria (asterisks) all others as dots. Adapted (in SVG!) from Woese Bacterial evolution 1987.

30S ribosomal subunit protein S1
S1 is the largest ribosomal protein, present in the small subunit of the bacterial ribosome. It has a pivotal role in stabilizing the mRNA on the ribosome. 3 In Gram-negative bacteria, the multi-domain protein S1 is essential for translation initiation, as it recruits the mRNA and facilitates its localization in the decoding center.

Translation through ribosomes,  amazing nano machines - Page 2 _pre-r12
Location of S1 within the 30S subunit.
(a) Surface representation of the 11.5-Å resolution cryo-EM map.
(b) X-ray structure of the 30S subunit, filtered to the resolution of the cryo-EM map and shown in the same solvent-side orientation. The area highlighted with a rectangle shows a large, extra mass of density in the cryo-EM map (a). (c and d) The difference map (red), obtained by subtracting the masses corresponding to only 30S ribosomal proteins in the x-ray and cryo-EM maps, is superimposed on the cryo-EM map (c) and on the filtered x-ray map of the 30S subunit
(d). In c, the 30S map is shown as a semitransparent surface, in which the difference density map is embedded. The S21 mass is marked with an arrow in c and d.

Protein S1 is the largest ribosomal protein, 68 kDa, present in the small subunit of the Escherichia coli 70S ribosome.  Protein S1 has been reported to be necessary in some cases for translation initiation and for translation elongation. It is the only ribosomal protein that has a high affinity for mRNA. As a ribosomal protein, S1 is strikingly atypical. 






1. https://en.wikipedia.org/wiki/16S_ribosomal_RNA
2. https://www.sciencedirect.com/science/article/pii/B9780081022689000057
3. Visualization of protein S1 within the 30S ribosomal subunit and its interaction with messenger RNA
https://www.pnas.org/content/98/21/11991
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288201/

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Protein folding, surprising mechanisms point to an arranged set up

https://reasonandscience.catsboard.com/t1661p25-translation-through-ribosomes-amazing-nano-machines#8052

Prebiotic protein folding is indeed a huge problem, since we know now that the ribosome has a helping hand in promoting the right folding. And when that does not occur, no deal. So you need a ribosome to have functional protein folds, but you need functional folds to make a ribosome. What came first ?

Proteins, in order to become functional, must fold into very specific 3D shapes, which happens right when they come out of the ribosome, where they are synthesized. Specific protein shape and conformation depends on the interactions between its amino acid side chains. For a protein to function it must fold into a resting state which is a complex three-dimensional structure.  If a protein fails to fold into its functional structure then it is not only without function but it can become toxic to the cell. As proteins fold, they test a variety of conformations before reaching their final form, which is unique and compact. Folded proteins are stabilized by thousands of noncovalent bonds between amino acids. A relatively small protein of only 100 amino acids can take some 10^100 different configurations. If it tried these shapes at the rate of 100 billion a second, it would take longer than the age of the universe to find the correct one. Just how these molecules do the job in nanoseconds, nobody knows. 1

If we take one of the smallest free living bacteria, they have about 1300 proteins, with an average of about 400 amino acids. If their amino acid sequence and arrangement were to emerge prebiotically, without the instructional information from a genome, more attempts would be required  than the number of atoms in the universe, to get the right set. Not considering all the inherent problems with this scenario, like the lack of mechanisms to select the right amino acid set used in life, and sorting out of the right-handed ones ( life uses only left-handed amino-acids ), the fact that some amino acids never have been found besides being synthesized in the Cell, this is a major problem. And so the fact, that the linking bonds of these polymers are peptide and ester bonds. In both cases, the polymerization reaction is thermodynamically uphill, with hydrolysis being favored. ( hydrolysis  means that any chemical reaction in which a molecule of water ruptures one or more chemical bonds )  How then can polymers be synthesized? For prebiotic scenarios, there is no compelling answer. In the cell, the monomers have been chemically activated by an input of metabolic energy so that polymerization is spontaneous in the presence of ribosomes that catalyze polymerization.  Catalyzing bond formation in the Ribosome comes out to be a very carefully engineered and precise process, where the surrounding ribonucleotides must be placed very precisely, at the right place. How do proteins fold from a linear sequence of amino acids into functional form, where they can operate as molecular machines ? 

Science has unraveled surprising and astonishing details of what mechanisms might be in place, answering this question. 

One of the most important mechanisms that play a vital role in the cell is the amino acid peptide bond formation during protein synthesis. It takes place in the so-called peptidyl transferase center, which is the reaction center in the Ribosome.  Peptide bond formation is by no means a simple, or trivial task. The process is so intriguingly complex, that a science paper in 2015 had still to admit that:  The process of peptide bond formation is of particular importance, being the heart of protein synthesis. 1 The detailed mechanism of peptidyl transfer, as well as the atoms and functional groups involved in this process are still in limbo. 

The ribosome speeds up the reaction rate and catalyzes peptide bond formation 10 million times faster than  compared to an uncatalyzed reaction.  The ribosome subunit, where the catalysis takes place, is called 23S ribosomal RNA. It has a length of  2904 nucleotides(in E. coli). 

A precise, minutely orchestrated arrangement of just two main players amongst these 2904 nucleotides is absolutely essential,  the interaction of ribose 2'-OH at position A2451 , and the 2’ hydroxyl of the P site substrate A76  . They are pivotal in orienting substrates in the active site for optimal catalysis, and play a key role in polypeptide bond formation. 

My comment: Consider this as an extraordinary engineering feat. Amongst 2905 nucleotides, just one is the main player interacting with another to promote this life essential reaction, and had to be positioned precisely in the right spot. 

Evidently, the positioning of all substrates, transition states, and ribosomal residues contributing to the concerted redistribution of charges must be tightly controlled to achieve efficient transpeptidation compatible with the observed in vivo rates of amino acid polymerization of about 20 amino acids per second. 

Molecular biology of the Cell, Alberts, 6th ed. pg. 369

Producing an overall speed of translation of 20 amino acids incorporated per second in bacteria. Mutant bacteria with a specific alteration in the small ribosomal subunit have longer delays and translate mRNA into protein with an accuracy considerably higher than this; however, protein synthesis is so slow in these mutants that the bacteria are barely able to survive.

Question: How could the right speed have been obtained with trial and error, if slow mutants do not survive? Had the speed not to be right from the beginning?

This 2'-OH renders almost full catalytic power. These data highlight the unique functional role of the A2451 2'-OH for peptide bond synthesis among all other functional groups at the ribosomal peptidyl transferase active site. Key in this reaction is the presence of a proton shuttling group.  The observed 100-fold reduction in the reaction rate by mutation of P-site A76 20-OH group  is indication of this group's activity during the peptidyl transfer reaction.

Remember this functional group, A2451. I will return to it at the end of this article.

Remarkably, as we will see in the following, protein folding is not only dependent on the amino acid sequence, or stabilizing forces. 

A paper reports:
Protein folding in living cells requires a mechanism of action through direct manipulation of the peptide backbone during polypeptide bond formation.  Considering the rotating motion of the tRNA 3’-end in the peptidyltransferase center of the ribosome, it is possible that this motion might introduce rotation to the nascent peptide and influence the peptide’s folding pathway. The 3’ terminus of the tRNA in the A-site of the ribosome peptidyl transferase center turns by nearly 180 degrees in every translation elongation cycle. Only a 45-degree swing is necessary to achieve the proper stereochemistry of the peptide bond formation; the function of the remaining portion of the turn is hypothesized to be needed to facilitate co-translational folding 1

Experimental results are in line with our  hypothetical mechanism through which the ribosome  directly altesr the conformations of proteins by applying mechanical force to the peptide backbone.  In vivo the peptide backbone can be manipulated into conformations that cannot be reached without assistance because they are either thermodynamically unstable or kinetically inaccessible. The results of our simulations thus demonstrate the feasibility of a protein folding mechanism during peptide bond formation.

My comment: This demonstrates that protein folding ( which is essential to get functional proteins ) is a complex, finely orchestrated process that depends not only on the correct amino acid sequence, and the decrease in Gibbs free energy, but also an active energy-dependent process. The mechanism of action of the ribosome (protein folding machine ). That means, without the concerted action of the ribosome, the original minimal proteome would never have formed prebiotically in absence of the ribosome, directly involved in the folding process.  The ability of any present-day protein to fold in isolation and without assistance not shared by most  proteins. Thus, the notion of an active, energy-dependent protein folding mechanism  in vivo reinforces the understanding of an intelligently bioengineered process  than the generally accepted evolutionary process, and that the ability of proteins to attain their native conformations must have evolved by natural selection of sequences that fold quickly and correctly (“evolution solved the protein folding problem” ) becomes more and more remotely possible. 

And more mechanisms are in play helping protein folding insider the ribosome:  
Some recently published results, include studies of the role of the exit tunnel in nascent chain folding.  For small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins. That the small zinc-finger domain ADR1a folds cotranslationally as the tether connecting it to the ribosome grows in length from ∼20 to ∼30 residues.  ADR1a buried deep in the vestibule of the exit tunnel, provides a clear demonstration that small proteins or protein domains can fold within the ribosome, as predicted by computational studies Although the zinc finger is one of the smallest independently folding protein domains, it has been estimated that ∼9% of all structural domains found in the PDB are less than 40 residues long, and ∼18% are less than 60 residues long. Folding of protein domains wholly or partly inside the exit tunnel may thus be not too uncommon, despite its relatively constrained geometry. But even MORE REMARKABLY: In the upper part of the tunnel, results suggest that A2062 and A2451 can communicate in both directions for translation stalling, mostly through dynamically coupled C2063, C2064, and A2450.

My comment:  This is truly awe-inspiring. The functional group A2451, which is not only of crucial importance as described above for peptyde bond catalysis, but when the translation process is stalled, it signals to a dynamically coupled group in the exit tunnel of the product, the polypeptide chain: " we have a problem here" !! and the ribosome takes action. 

Prebiotic protein folding is indeed a huge problem, since we know now that the ribosome has a helping hand in promoting the right folding. And when that does not occur, no deal. So you need a ribosome to have functional protein folds, but you need functional folds to make a ribosome. What came first ?

If all this is not evidence of a bioengineered process, i don't know, what is!!

Translation through ribosomes,  amazing nano machines - Page 2 P-site13

1. https://www.biorxiv.org/content/10.1101/2020.09.01.277582v1.full



Last edited by Admin on Sun Oct 11, 2020 8:45 am; edited 3 times in total

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Amazing surveillance pathways that rescue ribosomes lost in translation point to intelligently designed mechanisms

https://reasonandscience.catsboard.com/t2984-error-check-and-repair-during-messenger-rna-translation-in-the-ribosome-by-chance-or-design#8048

The final step of the central dogma is the most complex, where the information in RNA is translated to build proteins in the ribosome.  Ribosomes occasionally get stalled when faulty messenger RNA molecules are read, for Instance, for a messenger RNA that has broken and is thus is missing its stop codon. The ribosome uses an incredible peace of bio-engineering to rescue a stalled situation when they get stuck at the end of the truncated chain. They use a mechanism called Trans-translation. It is a ubiquitous bacterial mechanism for ribosome rescue in the event of translation stalling. This mechanism is a key component of multiple quality control pathways in bacteria that ensure proteins are synthesized with high fidelity in spite of challenges such as transcription errors, mRNA damage, and translational frame shifting. Trans-Translation is performed by a ribonucleoprotein complex. A strangely shaped RNA molecule mimics both a transfer RNA and a messenger RNA, restarting the process and cleaning up the mess. A proteolysis-inducing tag is added at the unfinished polypeptide, and facilitates the degradation of the aberrant messenger RNA. Trans-translation relies on two main factors: small stable 10S RNA (ssrA), an aminoacylated transfer-messenger RNA (tmRNA) with properties both of a tRNA and an mRNA; and SmpB (small protein B)

My comment: This is awesome. Wow!! How could random non-guided, non-intelligent mechanisms have foresight, and the knowledge of this problem of truncated messenger RNA's that do not have a stop codon, and a sophisticated mechanism to deal with it? This is a masterfully crafted salvage mechanism in order to prevent the cell to produce toxic polymer strands that would accumulate, and in the end, destroy the cell. This is an engineering marvel of extraordinary sophistication.

Translation through ribosomes,  amazing nano machines - Page 2 Transf10
Transfer-messenger RNA.
Transfer-messenger RNA (top ) includes a portion that mimics a transfer RNA ( red ) and a portion that mimics a messenger RNA ( magenta ), complete with a stop codon. It binds to stalled ribosomes ( bottom ), resuming synthesis using its own short message. Amazingly, this message encodes a small tag that is added to the end of the truncated protein, signaling to the cell that the protein is faulty and needs to be destroyed

Transfer-messenger RNA
https://en.wikipedia.org/wiki/Transfer-messenger_RNA

Transfer-messenger RNA (abbreviated tmRNA ) is a bacterial RNA molecule with dual tRNA-like and messenger RNA-like properties. The tmRNA forms a ribonucleoprotein complex (tmRNP) together with 
- Small Protein B (SmpB), 
- Elongation Factor Tu (EF-Tu), and 
- ribosomal protein S1. 
In trans-translation, tmRNA and its associated proteins bind to bacterial ribosomes which have stalled in the middle of protein biosynthesis, for example when reaching the end of a messenger RNA which has lost its stop codon. The tmRNA is remarkably versatile: it recycles the stalled ribosome, adds a proteolysis-inducing tag to the unfinished polypeptide, and facilitates the degradation of the aberrant messenger RNA

Biology of trans-Translation
The trans-translation mechanism is a key component of multiple quality control pathways in bacteria that ensure proteins are synthesized with high fidelity in spite of challenges such as transcription errors, mRNA damage, and translational frameshifting. trans-Translation is performed by a ribonucleoprotein complex composed of tmRNA, a specialized RNA with properties of both a tRNA and an mRNA, and the small protein SmpB. tmRNA-SmpB interacts with translational complexes stalled at the 3prime end of anmRNA to release the stalled ribosomes and target the nascent polypeptides and mRNAs for degradation. In addition to quality control pathways, some genetic regulatory circuits use transtranslation to control gene expression. Diverse bacteria require transtranslation when they execute large changes in their genetic programs, including responding to stress, pathogenesis, and differentiation. 1

Genes encoding tmRNA and SmpB are present throughout the bacterial kingdom.

Translation through ribosomes,  amazing nano machines - Page 2 Trans-10
trans-Translation removes all components of stalled translation complexes. 
tmRNA binds to SmpB and is aminoacylated by alanyl-tRNA synthetase (AlaRS). EF-Tu in the GTP state binds to alanyl-tmRNA, activating the complex for ribosome interaction. The alanyl-tmRNA/SmpB/EF-Tu complex recognizes ribosomes at the 3' end of an mRNA and enters the A-site as though it were a tRNA. The nascent polypeptide is transferred to tmRNA, and the tmRNA tag reading frame replaces the mRNA in the decoding center. The mRNA is rapidly degraded. Translation resumes, using tmRNA as a message, resulting in addition of the tmRNA-encoded peptide tag to the C terminus of the nascent polypeptide. Translation terminates at a stop codon in tmRNA, releasing the ribosomal subunits and the tagged protein. Multiple proteases recognize the tmRNA tag sequence and rapidly degrade the protein (box 3).



1. https://sci-hub.st/https://www.annualreviews.org/doi/10.1146/annurev.micro.62.081307.162948
2. https://sci-hub.st/https://www.nature.com/articles/nrm3457?proof=t

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