Chemical evolution of amino acids and proteins ? Impossible !! 

Chemical evolution of amino acids and proteins ? Impossible !! 

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

Chemical evolution of amino acids and proteins ? Impossible !!
https://www.youtube.com/watch?v=1L1MfGrtk0A

In order to have a minimal functional proteome one would have to assume that: 
1.  the conditions of the primitive atmosphere were known.
2.  Nitrogen and carbon in fixed form, necessary elements of amino acids, was readily available, and that all of the twenty amino acids used in life did form naturally ( disregarding the lifetime of ammonia which would be short because of its photochemical dissociation)
3.  Organosulfur compounds required in a few amino acids used in life would be readily available, even if in nature sulfur exists only in its most oxidized form (sulfate or SO4), and only some unique groups of prokaryotes mediate the reduction of SO4 to its most reduced state (sulfide or H2S)
4.  Billions of each amino acid would be readily available. ( even if eight proteinogenic amino acids were never abiotically synthesized under prebiotic conditions)
5.  The amino acids would be concentrated all together at one assembly site.
6.  There would be selected twenty, and not more or less amino acids to make proteins.
7.  Only the best suited would have been selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets inside proteins
8.  Nature did somehow "know" that the set of amino acids selected appears to be near ideal and optimal.
9.  The amino acids were only in homochiral, that is the left-handed configuration.
10. They would be pure, and without contaminating reactants, somehow avoiding the concomitant synthesis of undesired or irrelevant by-products.
11. They would be all bifunctional monomers with amino groups and carboxyl groups. AA's with unifunctional monomers (with only one functional group) would have been sorted out somehow.
12. They would remain stable, and not DEVOLVE to give uselessly complex mixtures, “asphalts”
13. They would be able to bond and polymerize by non-enzymatic means, without the ribosome
14. There are four different ways to bond AA's together by the side chains. if bonded to the wrong side chain, no deal. They would, somehow, bond together at the right place.
15. The polypeptide chain would not hydrolyze to its constituent amino acids.
16. In each trial, the average protein would be  400 amino acid  units in length
17. The rate to form and test each chain would be just one-third of a ten-million-billionth of a second!  This is around 150 thousand trillion times the normal speed in living things.
18. If a usable sequence were obtained, the action would stop so that it would be preserved, and shuffling would restart to obtain all proteins required for life.
19. 1/3 of all proteins once folded require chaperones, other proteins, that help the protein to fold into its proper, functional shape. They were not required for the first protein folds.  
20. The synthesized proteins would be able to merge and interlink into assembly lines and metabolic pathways, ready for working together in a living system.
21. Somehow, nature knew how to transition from prebiotic synthesis to cell synthesis of amino acids.  A minimum of 112 enzymes is required to synthesize the 20 (+2) amino acids used in proteins.
22. Why are amino acids used, as opposed to say hydroxy acids, thio acids, or amino sulphonic or amino phosphinic acids?
23. Why are N-unsubstituted a-monoalkyl amino acids used and not b-, g- or d-amino acids, a-dialkylamino acids, or N-alkyl-a-amino acids?

Unsolved issues:
Unsolved issues about the origin of amino acids on early earth:
How did unguided nondesigned coincidence select the right amino acids amongst over 300 ( known, but the number is theoretically limitless ) that occur naturally on earth? All life on Earth uses the same 20 ( in some cases, 22 genetically encoded) amino acids to construct its proteins even though this represents a small subset of the amino acids available in nature?
How would twenty amino acids be selected (+2)  and not more or less to make proteins?
How was the concomitant synthesis of undesired or irrelevant by-products avoided?
How were bifunctional monomers, that is, molecules with two functional groups so they combine with two others selected, and unfunctional monomers (with only one functional group) sorted out?
How were β, γ, δ… amino acids sorted out?
How did a prebiotic synthesis of biological amino acids avoid the concomitant synthesis of undesired or irrelevant by-products?
How could achiral precursors of amino acids have produced and concentrated only left-handed amino acids? ( The homochirality problem )?
How did the transition from prebiotic enantiomer selection to the enzymatic reaction of transamination occur that had to be extant when cellular self-replication and life began?
How did ammonia (NH3), the precursor for amino acid synthesis, accumulate on prebiotic earth, if the lifetime of ammonia would be short because of its photochemical dissociation?
How could prebiotic events have delivered organosulfur compounds required in a few amino acids used in life, if in nature sulfur exists only in its most oxidized form (sulfate or SO4), and only some unique groups of procaryotes mediate the reduction of SO4 to its most reduced state (sulfide or H2S)?
How did the transition from prebiotic enantiomer selection to the enzymatic reaction of transamination occur that had to be extant when cellular self-replication and life began?
How did natural events have foreknowledge that the selected amino acids are best suited to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets inside proteins?
How did nature select the set of amino acids which appears to be near-optimal in regard to size, charge, and hydrophobicity more broadly and more evenly than in 16 million alternative sets?
How did Amino acid synthesis regulation emerge? Biosynthetic pathways are often highly regulated such that building blocks are synthesized only when supplies are low.
How did the transition from prebiotic synthesis to the synthesis through metabolic pathways of amino acids occur? A minimum of 112 enzymes is required to synthesize the 20 (+2) amino acids used in proteins.

In order to have a functional protein, you need to have amino acids.
In order to have the amino acids used in life, you have to select the right ones amongst over 500 that occur naturally on earth.
To get functional ones, you need to sort them out between left-handed and right-handed ones ( the homochirality problem). Only left-handed amino acids are used in cells.
There is no selection process known besides the one used in cells by sophisticated enzymes, which produce only left-handed amino acids.
Amino acids used for life have amino groups and carboxyl groups. To form a chain, it is necessary to have the reaction of 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.
The useful amino acids would have to be joined and brought together at the same assembly site in enough quantity.
There are four different ways to bond them together by the side chains. if bonded to the wrong side chain, no deal.
The formation of amide bonds without the assistance of enzymes poses a major challenge for theories of the origin of life.
Instructional/specified complex information is required to get the right amino acid sequence which is essential to get the functionality in a vast sequence space ( amongst trillions os possible sequences, rare are the ones that provide function )
Before amino acids would join into a sequence providing functional folding, it would disintegrate if hit by UV radiation.
But even IF that would not be the case, most proteins become only functional, if they are joined into holo-enzymes, where various amino acid chains come together like lock and key.
If that would occur, the tertiary or quaternary structure in most cases would bear no function without the insertion of a co-factor inside the pocket, like retinal in the opsin pocket, forming rhodopsin.
But even IF there would emerge a functional protein on the early earth, by itself, it would be like a piston outside the engine block of an automobile. Many proteins bear only function once they are integrated in an assembly line, producing sophisticated molecular products used in life.
But even IF we had an assembly line of enzymes producing a functional product, what good would there be for that product, if the cell would not know where that product is required in the Cell?
For example, chlorophyll requires the complex biosynthesis process of 17 enzymes, lined up in the right order, each producing the substrate used by the next enzyme.  But chlorophyll has no function unless inserted in the light-harvesting antenna complex used in photosynthesis to capture light and funnel it to the reaction center.  
But even if that complex, chlorophyll and the LHC would be fully set up, they have no function without all over 30 protein complexes forming photosynthesis, used to make hydrocarbons, essential for all advanced life forms.  
Now, let's suppose all this would assemble by a freaky random accident on early earth, there would still be no mechanisms of transition from a prebiotic assembly, to Cell factory synthesis.

Tan; Stadler:  The Stairway To Life:
Countless biology textbooks describe the Miller-Urey experiment and others like it as strong evidence that life began spontaneously. This argument seemingly equates the simplicity of a handful of amino acids (formed by a natural process) with the unimaginable complexity of living organisms. This is like finding sand and concluding that microprocessors (computer chips based upon silicon) must be able to assemble spontaneously. Indeed, the chasm between simple organic molecules and living organisms is frequently dismissed in a single sentence. Take, for example, this quote from a popular biology textbook: “The first spark of life ignited when simple chemical reactions began to convert small molecules into larger, more complex molecules with novel 3-D structures and activities”. In his 2014 book, Undeniable, Bill Nye similarly applies “the spark of life” to dismiss complexity: “The origin of life just requires some raw material that could allow the spark of life to emerge”. Walt Disney made a movie about a wooden puppet that turned into a boy through a spark of life. Perhaps such fantasy inspired our current biology textbooks and Bill Nye because these statements are certainly not based on scientific evidence or rational thought. In The Vital Question, a 2015 book that Bill Gates praised as “an amazing inquiry into the origins of life,” biochemist Nick Lane expects his readers to join him in dismissing the great complexity separating simple building blocks and living cells: The formation of organic matter from H2 and CO2 is thermodynamically favoured under alkaline hydrothermal conditions, so long as oxygen is excluded…This means that organic matter should form spontaneously from H2 and CO2 under these conditions. The formation of cells releases energy and increases overall entropy! The average reader of The Vital Question may not have noticed the colossal leap that occurred in the last sentence, where Lane equates spontaneous formation of organic building blocks with the spontaneous formation of cells. This could indeed be possible if cells were “nothing more than a shapeless, mobile, little lump of mucus or slime, consisting of an albuminous combination of carbon,” as thought by Haeckel in the late nineteenth century, but each new year of research exposes previously unimagined layers of cellular complexity, even among the simplest known forms of life. Bestselling author Dan Brown, in his 2017 book Origin, includes a respected scholarly character Robert Langdon who concludes, “Life arose spontaneously from the laws of physics”. Addy Pross, a professor of chemistry at Ben Gurion University, concludes the following in his 2012 book, What is Life?: “Life then is just the chemical consequences that derive from the power of exponential growth operating on certain replicating systems”. Jeremy England, a professor of physics at MIT who also happens to appear in Dan Brown’s Origin, similarly sweeps all the complexity of life under the rug with one sentence: “You start with a random clump of atoms, and if you shine light on it for long enough, it should not be so surprising that you get a plant” . Carl Sagan offered similar words, which are strikingly discordant with all observable evidence: “The origin of life must be a highly probable affair; as soon as conditions permit, up it pops!” . Daily news articles on astronomy and astrobiology barrage us with suggestions that life probably exists on other planets. These articles lead us to believe that the simple discovery of water on a planet virtually guarantees the spontaneous formation of life. A reality check is long overdue. The fantastic complexity of all known life-forms stands in stark contrast to what our schools are teaching, what some scientists believe, and what popular media suggests.


Chemical evolution of amino acids and proteins ? Impossible !!
https://www.youtube.com/watch?v=1L1MfGrtk0A

The problem of getting nitrogen to make amino acids and DNA on early earth   2:41
The problem of getting all amino acids used in llife by origin of life experiments 4:20
The problem of selecting 20 amino acids prebiotically out of hundreds supposedly existing on early earth. 6:08
The problem of concentrating the amino acids used in life at one assembly site.  7:15
The problem of understanding why life uses 20 amino acids, and not more or less. 9:00
The problem of homochirality 12:23
The problem of amino acid synthesis regulation 13:43
The problem of peptide bonding of amino acids to form proteins 14:12
The problem of linking the right amino acid side sequence together  17:15  
The problem of getting the right forces to stabilize proteins - essential for their correct folding 19:32
The problem of hierarchical structures of proteins 19:50


Scripps Research Institute: [A chemical clue to how life started on Earth AUGUST 1, 2019
https://www.sciencedaily.com/releases/2019/08/190801093310.htm

Claim: "In the prebiotic Earth, there would have been a much larger set of amino acids," says Leman, who also is scientific collaborator at the Center for Chemical Evolution. "Is there something special about these 20 amino acids, or did these just get frozen at a moment in time by evolution?"

The new study suggests that life's dependence on these 20 amino acids is no accident. The researchers show that the kinds of amino acids used in proteins are more likely to link up together because they react together more efficiently and have few inefficient side reactions.
https://www.universetoday.com/143056/all-life-on-earth-is-made-up-of-the-same-20-amino-acids-scientist-now-think-they-know-why/

Response:
This is a classic example to how methodological naturalism drives to the attempt to provide explanations, which reveal to be nothing more than pseudo-scientific nonsensical explanations.
First of all: The authors neglect and obfuscate the fact that twelve of the twenty life essential amino acids, which are synthesized in hypercomplex metabolic pathways in the Cell, which are central to all life, namely: Cysteine Histidine Lysine Asparagine Pyrrolysine Proline Glutamine Arginine Threonine Selenocysteine Tryptophan Tyrosine have never been synthesized in the lab.

Claim: Scientists believe that there were over 500 naturally-occurring acids present on Earth during the Hadean Eon. As Loren Williams, a professor of biochemistry at Georgia Tech, explained:

“Our idea is that life started with the many building blocks that were there and selected a subset of them, but we don’t know how much was selected on the basis of pure chemistry or how much biological processes did the selecting.

Response: There is no reasonable natural unguided mechanism selecting twenty amino acids out of a pool of 500 supposedly existing. Why would it select anyway? See, the word " selecting" is misused so much today, and it is ignored that selecting is something that conscious minds do with a specific purpose. Mindless processes do not select anything in the literal meaning of the word.  

Even IF they were likely to link up together because they react together more efficiently and have few inefficient side reactions, that says nothing about the fact that functional sequences in sequence space are EXTREMELY rare.

Functionally Acceptable Substitutions in Two a-Helical Regions of X Repressor
"The estimated number of sequences capable of adopting the h repressor fold is still 10^63 an exceedingly small fraction, about one in of the total number of possible 92-residue sequences."
http://sci-hub.tw/https://onlinelibrary.wiley.com/doi/pdf/10.1002/prot.340070403

Truth said: The information barrier is a problem that CANNOT be solved, and puts all abiogenesis explanations into the realm of SCIENCE FICTION. The ONLY reasonable, logical, and sound inference is that an immensly intelligent, powerful, eternal creator, created a universe, suited to host life, and created life in accordance to his eternal purposes. The fact that we do not know how the interface mind/matter works, says nothing about the possibility/impossibility.

Eliminative inductions argue for the truth of a proposition by arguing that competitors to that proposition are false. Provided the proposition, together with its competitors, form a mutually exclusive and exhaustive class, eliminating all the competitors entails that the proposition is true. Since either there is a God, or not, either one or the other is true. As Sherlock Holmes famous dictum says: when you have eliminated the impossible, whatever remains, however not fully comprehensible, but logically possible, must be the truth. Eliminative inductions, in fact, become deductions.

Amino acids used for life have amino groups and carboxyl groups. To form a chain, it is necessary to have the reaction of 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.

The chart from Richard E. Dickerson's article, "Chemical Evolution and the Origin of Life," published in Scientific American in 1978, provides insights into the yield of one of Stanley Miller's experiments, which aimed to simulate conditions that could have led to the formation of organic compounds necessary for life. In Miller's experiment, 59,000 millimoles (mmol) of carbon in the form of methane were used as a starting material.

The main unifunctional products obtained from this experiment were as follows:

Formic acid: 2,330 mmol
Lactic acid: 310 mmol
Acetic acid: 150 mmol
Propionic acid: 130 mmol

In addition to the organic acids, four amino acids that are found in modern proteins were also produced in the experiment. The quantities of these amino acids obtained were:

Glycine: 630 mmol
Alanine: 340 mmol
Glutamic acid: 6 mmol
Aspartic acid: 4 mmol

Stanley Miller's pioneering experiments, including the one mentioned in the article, have contributed significantly to our understanding of how organic compounds, such as amino acids and organic acids, could have formed on early Earth and potentially led to the emergence of life.

The presence of both amino groups and carboxyl groups in amino acids is indeed essential for the formation of peptide chains. The formation of peptide bonds between amino acids requires the reaction of bifunctional monomers, meaning molecules that possess two functional groups capable of participating in the bonding process. In this case, amino acids act as the bifunctional monomers. However, the problem arises when considering the abundance of unifunctional molecules, those with only one functional group, in comparison to bifunctional molecules in prebiotic simulations. All 'prebiotic simulation' experiments produce at least three times more unifunctional molecules than bifunctional molecules. This poses a challenge for the formation of long polymers, such as proteins. If unifunctional monomers react with the growing chain at the end, they will essentially terminate the chain's growth at that point because they cannot form further bonds. If a significant fraction of the available monomers are unifunctional, it becomes difficult for long polymers to form because the unifunctional monomers will tend to hinder further growth. This scenario contradicts the requirements for the formation of complex polymers like proteins, which necessitate a higher abundance of bifunctional monomers. The imbalance in favor of unifunctional molecules in prebiotic simulations makes it challenging to explain the emergence of long, functional chains in a plausible and efficient manner. This discrepancy between the abundance of bifunctional and unifunctional molecules raises questions about the plausibility of the proposed mechanisms for the origin of life.

The problem of interacting side chains

The prebiotic polymerization of amino acids, which is a key process in the origin of life, presents some challenges due to the interactions between the side chains of amino acids. These interactions can hinder the formation of long, linear chains and affect the overall efficiency of the polymerization reaction. One of the primary challenges arises from the fact that the side chains of amino acids can react with each other, forming bonds between them instead of allowing the formation of peptide bonds that link amino acids together in a linear chain. This side-chain reactivity can lead to the formation of cyclic structures or branching in the resulting polymers, rather than the desired linear sequences. These side-chain interactions can limit the extent of polymerization and the production of long, biologically relevant chains. The presence of branching or cyclic structures can disrupt the formation of stable secondary structures like alpha-helices and beta-sheets, which are important for the proper folding and functioning of proteins. Furthermore, the side-chain interactions can also affect the stability and solubility of the resulting polymers. Depending on the nature of the side chains involved, they can introduce structural constraints or hydrophobic interactions that make the polymers less stable or less soluble in water. The consequence of side-chain interactions during prebiotic polymerization is that it can limit the formation of long, linear sequences of amino acids necessary for the development of functional proteins. The complexity and diversity of proteins as we observe them in living organisms today is a result of the precise arrangement and sequence of amino acids, which allows for specific interactions and functions. 

Prebiotic nature requires that polymerization reactions occur selectively between specific amino acids. However, in a prebiotic environment where different amino acids are present in varying concentrations, achieving selectivity in the formation of peptide bonds between the desired amino acids is challenging. During the polymerization reaction, reactive intermediates are formed. These intermediates are unstable under prebiotic conditions and can be easily hydrolyzed before they can join with other amino acids. The prebiotic synthesis of amino acids may be limited in primitive environments. While the synthesis of simple amino acids has been demonstrated in laboratory conditions simulating early Earth conditions, obtaining all the necessary amino acids for protein formation remains a challenge.  Prebiotic polymerization reactions of amino acids are generally slow in the absence of suitable catalysts.  Kinetic barriers: Polymerization reactions face kinetic barriers, meaning the reactions may be energetically unfavorable or have high activation energies. Overcoming these barriers in a prebiotic setting, where energy sources may be limited, is a significant challenge. Prebiotic environments are complex and may contain various impurities and reactive species that can interfere with the polymerization process. Competing reactions, such as hydrolysis or non-specific bonding, can reduce the yield and efficiency of peptide bond formation.  In modern biological systems, enzymes act as templates to guide and accelerate the polymerization of amino acids. However, in a prebiotic context, the emergence of such template molecules is a fundamental question. The spontaneous formation of well-defined templates that can facilitate polymerization selectively is a significant challenge.  Living organisms on Earth primarily use left-handed (L-amino acids) in protein synthesis. However, prebiotic reactions often produce both left- and right-handed (D-amino acids) forms. Achieving the selective production of L-amino acids and maintaining homochirality is crucial for the formation of functional proteins.  Prebiotic polymerization reactions are highly sensitive to environmental conditions such as pH, temperature, presence of metal ions, and redox potential. Recreating the specific environmental conditions of early Earth and understanding how they influenced the polymerization process is a complex task.  Demonstrating prebiotic polymerization reactions on a laboratory scale is one thing, but scaling up these reactions to a level where they can account for the formation of polymers and proteins in a primordial soup scenario is a considerable challenge.

Chemical evolution of amino acids and proteins ? Impossible !!
https://www.youtube.com/watch?v=1L1MfGrtk0A




Origin of life assumptions started with the idea that the environment where life emerged was a complex solution of abiogenic organic molecules either in the primitive ocean of some warm little pond,  including amino acids and sugars—in other words, all the monomers required for the synthesis of biopolymers.


In a letter to his friend J.D. Hooker, Darwin wrote in 1871:

But if (& oh what a big if) we could conceive in some warm little pond with all sorts of ammonia & phosphoric salts,—light, heat, electricity &c present, that a protein compound was chemically formed, ready to undergo still more complex changes


The best-known theory is the  spontaneous generation, in other words, abiogenesis, by a “Prebiotic soup”, a theory hypothesized by Oparin in 1924 (Oparin, 1957).



In this theory, organic compounds were created in a reductive atmosphere from the action of sunlight and lightning. 


It was claimed that the atmosphere was primarily anoxic, consistent  of ammonia, methane, carbon dioxide and water vapor.


The compounds were then dissolved in the primitive ocean, concentrated, and underwent polymerization until they formed “coacervate” droplets. The hypothesis was an enormous success, first of all, among the adherents of neo-Darwinism.


The droplets supposedly grew by fusion with other droplets, were split into daughter droplets by the action of tidal waves, and developed the ability to catalyze their own replication, which eventually led to the emergence of life


According to the scientific narrative, it is hypothesized that Amino acids  emerged on Early earh, between 3.5 and 4 billion years ago, through chemical evolution by chemical synthesis, or better, chemical lucky accidents.  


Scientists now recognize twenty-two amino acids as the building blocks of proteins: the twenty common ones and two more, selenocysteine and pyrrolysine.





The problem of getting nitrogen to make amino acids and DNA on early earth

 


As implied by the word (amine), the essential key atom in amino acid composition is nitrogen, which is included in all enzymes and genes. The ultimate source of nitrogen for the biosynthesis of amino acids is abundant atmospheric nitrogen (N2), a remarkably inert molecule. 

Thus, a fundamental problem for biological systems is to obtain nitrogen in a more usable form. This problem is solved by certain microorganisms capable of reducing the inert N = N triple-bond molecule of nitrogen gas to two molecules of ammonia in one of the most amazing reactions in biochemistry. 


This bond is extremely difficult to break because the three chemical bonds need to be separated and bonded to different compounds. Nitrogenase, a veritable molecular sledgehammer, belongs to the only family of enzymes capable of breaking this bond, carrying out nitrogen fixation. But on early earth, biosynthesis of fixed nitrogen was not available.

For the origin of life, an abiotic source of biochemically accessible nitrogen, especially reduced nitrogen, is necessary.  There are proposals as for example UV-driven chemistry which is constructive for synthesizing and activating nucleotides and amino acids, but is destructive for more complex organic systems, such as, for example, DNA strands.


The problem of getting all amino acids used in llife by origin of life experiments


In 1953, Stanley Miller, a PhD student at the Uni of Chicago, and his supervisor, the  Nobel Prize winner Harold Urey,  did one of the most famous experiments in our story. They took  chemicals that he considered might be present in the atmosphere of the early Earth 

They ran water, methane, ammonia, and hydrogen in a sealed flask with a pair of electrodes to produce a spark, and from those simple building blocks discovered that more complex compounds, such as amino acids, were spontaneously produced. 

Various biological chemicals were found – glycine ( the simplest amino acid ) plus one of two other chemicals of interest.


After Millers death in 2007, the so called " volcano in the bottle " experiment was performed, and in total, 22 amino acids were identified. 


And the Secular Humanist Society heralded  that ALL 20 of the amino acids found in proteins – plus a few others, were produced. 


The reanalysis found indeed twenty two amino acids and five amines in the vials. But eight of the proteinogenic amino acids, that is the ones used in living systems, were never produced - in none of the experiments.

Cysteine, 
Histidine, 
Lysine, 
Asparagine, 
Glutamine, 
Arginine, 
Tryptophan, 
tyrosine 


have not been produced in any miller urey experiment. Nor do they occur naturally on earth   







As the building blocks of proteins, amino acids are linked to almost every life process, and as such, essential for life. Amino acids have several functions. Their primary function is to act as the monomer unit in protein synthesis.


The problem of selecting 20 amino acids prebiotically out of hundreds supposedly existing on early earth. 



In order to have the amino acids used in life, the twenty right ones amongst over 500 that occur naturally on earth would have had to be selected. 


If we suppose that the twenty used in life were ready available, how could that selection process have occured without guidance ? The article above askes : Why did life select just 20 amino acids when 500 occurred naturally on the Hadean Earth ? 

That is of course an invalid nonsensical question, since the selection of the right twenty amino acids is a prerequisite for life to start.  But also the claim that the 20 used in life were selected amongst 500 naturally occuring amino acids is misleading. 


As mentioned previously, eight of the twenty amino acids used in life have never been produced in any laboratory experiment, and aren't either encountered on earth naturally, and neither on meteorites. 


The problem of concentrating the amino acids used in life at one assembly site.



Polymer formation in aqueous environments would most likely have been necessary on early Earth because water would have been the reservoir of amino acid precursors needed for protein synthesis. 

The desired reagents would be extremely dilute in the ocean. And there was no mechanism in existence to concentrate amino acids to one place to start polymerization reactions. 

But then, even if that hurdle would be overcome, the next problem arises: Careful experiments done in an aqueous solution with very high concentrations of amino acids demonstrate the impossibility of significant polymerization, that is the production of proteins in this environment.


But even worse than that Amino acids tend to fall apart in water, not join. Even if there were billions of simultaneous trials as the billions of building block molecules interacted in the oceans, or on the thousands of kilometers of shorelines that could provide catalytic surfaces or templates, 


even if, as is claimed, there was no oxygen in the prebiotic earth, then there would be no protection from UV light, which would destroy and disintegrate prebiotic organic compounds.


A common argument is that amino acids could have been generated in hydrothermal vents, deep in the ocean, far from sunlight. hydrothermal vents could have been the primordial hatcheries of life.



Stanley Miller gave a clear answer: Submarine vents don't make organic compounds, they decompose them. 



The problem of understanding why life uses 20 amino acids, and not more or less.



Another relevant question is: Why are these twenty, in some cases, twenty two amino acids used in life, and not another set ? 


Why 20 and not 10 or 30? And why those particular 20? Forming soluble, stable protein structures with close‐packed cores are essential to stabilize proteins and to form a rigid structure with well-defined binding sites. and that requires the variety of amino acids used in cells. 

A selection of different hydrophobic amino acids permit more options to build a closed protein core and a pocket fit to permit the performance of a variety of enzymatic reactions. 

On the other hand, proteins required on the surface for example of cell membranes require straight chains and polar like arginine and glutamic acid.



Scientists have found that the set that is used by biology has a number of surprisingly non-random properties that stand out very clearly.


The paper: Frozen, but no accident – why the 20 standard amino acids were selected, concluded remarkably: We find that there are excellent REASONS for the selection of every amino acid. Rather than being a frozen accident, the set of amino acids
SELECTED appears to be near ideal.



Another paper of Nature magazine  Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids,  reported in 2015: We drew one hundred million random sets of 20 amino acids from our library of 1913 structures and compared their coverage of three chemical properties: 


size, charge, and hydrophobicity, to the standard amino acid alphabet.  We measured how often the random sets demonstrated better coverage of chemistry space in one or more, two or more, or all three properties.


In doing so, we found that better sets were extremely rare. In fact, when examining all three properties simultaneously, we detected only six sets with better coverage out of the 100 million possibilities tested.

That’s quite striking: out of 100 million different sets of twenty amino acids that they measured, only six are better able to explore “chemistry space” than the twenty amino acids that life uses.


That suggests that life’s set of amino acids is finely tuned to one part in 16 million. The problem here is that molecules and an arrangement of correctly selected variety of amino acids would bear no function until life began.

Only a conscient intelligent agent with foresight and reasoning could select for specific distant purposeful goals. Random, unguided events produce only chaotic structures. Science is absolutely clueless about how the optimal set  could have emerged prebiotically and without a guiding hand.


The problem of homochirality


Most molecules of life are homochiral, that is, they possess the same handedness or chirality. Homochirality of biological molecules is a signature of life. The  chirality or sense of handedness of the amino acid molecules is an important problem.

Figure above shows two versions, one is left handed, the other right handed. Each contains exactly the same number of elements with the same types of chemical bonds, and yet they are the mirror image of each other. A molecule that is not superimposable on its mirror image is called chiral. 


The handedness of biological molecules such as amino acids or nucleotides plays a role in their functionality. In proteins, only left handed amino acids can be incorporated. 




Cells, for instance, use complex molecular protein machines to synthesize amino acids only in left handed form. 



In nature, however, amino acids exist in chiral form. That means, both, left and right handed. There was no mechanism to sort them out on early earth, and group only left handed amino acids that then would be used to produce proteins. 


The problem of amino acid synthesis regulation

 



Biosynthetic pathways in living cells are often highly regulated such that building blocks are synthesized only when supplies are low.


Feedback mechanisms ensure that all 20 amino acids are maintained in sufficient amounts for protein synthesis and other processes. Obviously, such regulation did not exist prior the advent of modern cells.


The problem of peptide bonding of amino acids to form proteins

 


The formation of amide bonds without the assistance of enzymes poses a major challenge.



Given an ocean full of small molecules of the types  to be produced on pre-biological earth with the types of processes postulated by the origin of life enthusiasts, the next question is about polymerization. There are many different problems confronted by any proposal. 



Polypeptides are polymers of amino acids. In other words, many amino acids are chained and linked together via dehydration reactions that form peptide bonds between them. 

Polymerization is a reaction in which water is a product. Thus it will only be favoured in the absence of water. The presence of precursors in an ocean of water favours depolymerization of any molecules that might be formed. 




A peer reviewed paper published in 2014 tried to answer the question of prebiotic polymerization on early earth. 



To which Evolution News gave ten reasons why the proposals are not sound. 



Another problem is the fact that high activation energies are required for amide bond formation, beside the fact that direct peptide bond formation is slow unless high temperature or activating agents are used.



The problem of linking the correct amino acid side-chains together


There are four different ways to bond amino acids together by the side chains. Ff bonded to the wrong side chain, no deal.


Proteins are linear polymers formed by linking the α-carboxyl group of one amino acid to the α-amino group of another amino acid. To form a chain, it is necessary that only bifunctional monomers react together, 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.


Polymers can adopt various chain structures. Linear, branched, cross-linked, or networked. Proteins are linear homopolymers, while peptide polymers branched. There is no restriction of amino acids bond and form any of the different polimer structures. 


But only homopolymerisation permits the formation of functional primary structures used in proteins. Obviously, there was no natural selection of the right formation on the prebiotic earth. 


The problem of linking the right amino acid side-chanis together




In the same sense as the sequence of alphabetic letters are required to write words, the right sequence of amino acids are required to make functional proteins. 

This is truly fascinating: In the same sense as the instructional complex blueprint specifies how to make each gearwheel of a watch, and ultimately, the watch itself, the genetic code instructs the right amino acid sequence to make functional proteins. 

If we consider that there were no molecular cell machines to make proteins, no evolution, no mutations nor natural selection prior to functional cells and dna replication, how could the right sequence of a  minimal set of at least 500 proteins required for life have been specified, if not by an intelligent agency ? 

We only know of intelligence producing instructional information to make machines and factories for specific goals and purposes. 

Ribonuclease proteins are found in all domains of life, and it is claimed that they were present in LUCA, the last universal common ancestor of life, and as such, life-essential.  They are the simplest RNA proteins, and use 124 amino acids, 19 of the 20 different ones essential for life. 


The table demonstrates the catastrophically low probability of getting functional, meaningful amino acid sequences and as consequence, functional proteins, by random, unguided self-assembly spontaneously by orderly aggregation and sequentially correct manner without external direction


Amino acids may be the building blocks of proteins, but there is a world of difference between building blocks and an assembled structure. 


Just as the discovery of a pile of bricks is no guarantee that a house lies around the corner, so a collection of amino acids is a long, long way from the sort of large, specialized molecules such as proteins that life requires.




The problem of getting the right forces that stabilize proteins - essential for their correct folding



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.



The problem of hierarchical structures of proteins







Even if somehow a polypeptide chain in a functional sequence would emerge and fold into a form that later can be useful in the cell, that does not explain how to get to proteins which use not rarely several chains. 



Most proteins become only functional, if they are joined into holo-enzymes, where various amino acid chains come together like lock and key. 

Some proteins complexes use over 50 chains or subunits to form a highly complex molecular protein machine. And each subunit must fit precisely to interact correctly with other subunits or protein chains. 





Ribosomes for example which are veritable  macromolecular factories, are life essential, and found in all living cells. They are the factory which produce  biological protein synthesis by translating the genetic Code, and had to be fully developed when self-replication and life started.


Each ribosome contains around 80 proteins which work together like a various machine parts in a joint venture. It exerts far tighter quality control than anyone ever suspected over its precious protein products. and discarts error-laden proteins 10,000 times faster than it would normally release error-free proteins.

But even IF there would emerge a functional ribosome factory on the early earth, by itself, it would be like a piston outside the engine block of an automobile. Many proteins bear only function once they are integrated in an assembly line, producing sophisticated molecular products used in life.


To make proteins, and direct and insert them to the right place where they are needed, requires systematic cooperation. 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 makes its origin an irreducible  catch22 problem

In order for evolution to work, this awe inspiring robot-like working machinery and assembly line must be in place, fully operational. So the origin of this machinery cannot be explained through evolution.


All it is left as alternative explanation to intelligent design, are random chemical reactions. Does that make sense ?
 
Now, let's suppose all this would assemble by a freaky random accident on early earth, there would be no mechanism of transition from a prebiotic assembly, to Cell factory synthesis.


Eugene V. Koonin, The Logic of Chance: page 219
The emergence of cells is the epitome of the problems encountered by all explanations of the evolution of complex biological structures.  A succession of exceedingly unlikely steps is essential for the origin of life, from the synthesis and accumulation of nucleotides to the origin of translation; through the multiplication of probabilities, these make the final outcome seem almost like a miracle. Among modern biological entities, we do not see any intermediates between macromolecules and cells, and to imagine how such intermediates might operate is a huge challenge.


Lynn Margulis:
To go from a bacterium to people is less of a step than to go from a mixture of amino acids to a bacterium.



Now consider that we have discussed only the  prebiotic origin of amino acids and proteins. 


There is still the question of how phospholipids emerged to make cell membranes, RNA and DNA to make genes, and carbohydrates to make energy.


And to go from the basic building blocks of life, to a fully self replicating cell, is still a looong way to go.

1. Even in a primordial  self replicating cell, a  pathway of 25  steps, using complex specified enzymes, and error check and repair mechanisms to secure high findelity  is required to make proteins.
2. But the very same process is required, to make these enzymes, that make proteins. That is a chicken & egg, or catch22 problem.
3. The best explanation of its origin seems not  a gradative random  process, but instant creation by an intelligent creator.

Question: In how many ways can the side chain of an amino acid be bond to the central carbon atom ?
Reply: The side chain of an amino acid, also known as the R-group, can be bonded to the central carbon atom in several ways. The specific bonding pattern depends on the nature and chemical properties of the amino acid. 

Here are the common types of bonds formed by the side chain with the central carbon atom:

Aliphatic Side Chains: Aliphatic side chains are composed of carbon and hydrogen atoms and can have different bonding patterns, including:

a. Alkyl Chains: These side chains consist of straight or branched carbon chains. Examples include glycine (which has a hydrogen atom as the side chain), alanine, valine, leucine, and isoleucine.

b. Hydroxyl Group: Serine and threonine have a hydroxyl (-OH) group attached to the carbon chain.

Aromatic Side Chains: Aromatic amino acids have a benzene ring in their side chains. The bonding patterns include:

a. Phenylalanine: The side chain of phenylalanine is a simple benzene ring.

b. Tyrosine: Tyrosine contains a hydroxyl (-OH) group attached to the benzene ring.

c. Tryptophan: Tryptophan has a complex side chain that includes a fused ring system.

Sulfur-Containing Side Chains:

a. Cysteine: Cysteine contains a thiol (-SH) group in its side chain, which can form disulfide bonds with another cysteine residue.

b. Methionine: Methionine has a sulfur atom attached to an alkyl chain.

Acidic and Basic Side Chains:

a. Acidic Side Chains: Aspartic acid and glutamic acid have carboxyl (-COOH) groups as side chains, which can be deprotonated to form negatively charged carboxylates.

b. Basic Side Chains: Lysine, arginine, and histidine have basic properties due to amino groups or imidazole groups in their side chains. These side chains can be positively charged under certain pH conditions.

Question: How many binding sites are on the central carbon atom?
Reply:  The central carbon atom in an amino acid typically has four binding sites. These binding sites are occupied by four different groups or atoms, which include:

Amino Group: The amino group (-NH2) is one of the groups bound to the central carbon atom. It consists of a nitrogen atom bonded to two hydrogen atoms.

Carboxyl Group: The carboxyl group (-COOH) is another group bound to the central carbon atom. It consists of a carbon atom doubly bonded to an oxygen atom and singly bonded to another oxygen atom, which is also bonded to a hydrogen atom.

Hydrogen Atom: The central carbon atom is also bound to a hydrogen atom (H). This hydrogen atom is usually not explicitly shown in the chemical representation of amino acids.

Side Chain (R-group): The fourth binding site on the central carbon atom is occupied by the specific side chain or R-group of the amino acid. The nature and composition of the side chain vary among different amino acids, giving each amino acid its unique properties.

It's important to note that the central carbon atom in an amino acid is a chiral center, meaning it is bonded to four different groups. This property gives rise to the existence of two stereoisomers (L and D forms) for most amino acids, except for glycine, which does not have a chiral center.

Question: Is it possible to have carbon atoms with more or less binding sites than four?
Reply: Yes, it is possible for carbon atoms to have more or less than four binding sites. Carbon is tetravalent, meaning it typically forms four covalent bonds in organic chemistry. However, there are certain circumstances where carbon can have different bonding patterns.

Carbon with Fewer Binding Sites: Carbon atoms can have fewer than four binding sites by forming double or triple bonds with other atoms. For example, in a carbon-carbon double bond (C=C), each carbon atom is bound to three other atoms or groups. Similarly, in a carbon-carbon triple bond (C≡C), each carbon atom is bound to two other atoms or groups.

Carbon with More Binding Sites: Carbon atoms can have more than four binding sites when they form bonds with additional atoms or groups. This occurs in cases where carbon forms bonds with elements such as nitrogen, oxygen, or sulfur, which can contribute more than one bond to the carbon atom. Examples include carbon dioxide (CO2), where a carbon atom is bound to two oxygen atoms, and carbon disulfide (CS2), where a carbon atom is bound to two sulfur atoms.

Additionally, carbon atoms can participate in coordination complexes where they form additional bonds with metal ions, resulting in carbon having more than four binding sites.

Question:  Why do proteins need both, alpha helices, and beta sheets?
Reply: Proteins require a combination of alpha helices and beta sheets to achieve a diverse range of functions and structural stability. Here are a few reasons why proteins incorporate both these secondary structures:

Structural stability: Alpha helices and beta sheets provide structural stability to proteins. Alpha helices form stable, compact structures due to the extensive hydrogen bonding between the backbone atoms, allowing proteins to maintain their overall shape and rigidity. Beta sheets, on the other hand, contribute to stability by forming extended, sheet-like structures through hydrogen bonding between adjacent strands. The combination of alpha helices and beta sheets helps proteins withstand various environmental conditions and maintain their structural integrity.

Functional domains: Many proteins have specific regions or domains that are responsible for carrying out their functions. Alpha helices and beta sheets can form distinct structural motifs within these domains, facilitating specific interactions and molecular recognition. For example, alpha helices can participate in protein-protein interactions, DNA binding, or membrane-spanning regions, while beta sheets can form ligand-binding sites or enzymatic active sites. The presence of both alpha helices and beta sheets allows proteins to have diverse functional capabilities.

Flexibility and dynamics: Proteins often need to undergo conformational changes or exhibit flexibility to perform their biological roles. Alpha helices and beta sheets can act as flexible elements within a protein structure, enabling movement and flexibility in certain regions. These structural elements can bend, twist, or undergo subtle rearrangements, allowing proteins to adapt to different functional states or interact with other molecules.

Scaffold for tertiary structure: The combination of alpha helices and beta sheets provides a scaffold for the overall tertiary structure of proteins. Alpha helices and beta sheets can be arranged in various combinations and orientations, creating a three-dimensional fold unique to each protein. This folded structure is crucial for protein stability, proper folding, and the formation of active sites or binding pockets.

By incorporating both alpha helices and beta sheets, proteins can achieve a wide range of structural conformations, functional capabilities, and dynamic behaviors. The precise arrangement and combination of these secondary structures contribute to the diversity and complexity observed in the vast repertoire of proteins found in living organisms.

Question: What dictates the formation of alpha helices, and beta sheets?
Reply: Alpha helices are formed by right-handed coiling of the protein chain, where the backbone hydrogen bonds stabilize the helical structure. The formation of alpha helices is dictated by the regular arrangement of amino acids, specifically those with a propensity for helical conformation. The amino acid residues commonly involved in alpha helices are alanine, leucine, glutamate, and glutamine, among others. The repeating pattern of hydrogen bonds between the carbonyl oxygen of one amino acid residue and the amide hydrogen of another amino acid residue within the helix stabilizes its structure.

On the other hand, beta sheets are formed by adjacent protein strands that align with each other, and hydrogen bonds form between the amino acid residues in adjacent strands. The arrangement of these strands can be either parallel or antiparallel, depending on the directionality of the protein chains. The amino acid residues involved in beta sheets include glycine, alanine, valine, and isoleucine, among others. The hydrogen bonds between the backbone atoms of amino acid residues stabilize the beta-sheet structure.

It is important to note that alpha helices and beta sheets are distinct and different from each other in terms of their backbone conformation and hydrogen bonding patterns. Alpha helices have a coiled or helical structure, while beta sheets have an extended or sheet-like structure.

Mikhail Makarov: Early Selection of the Amino Acid Alphabet Was Adaptively Shaped by Biophysical Constraints of Foldability February 24, 2023

Claim: Whereas modern proteins rely on a quasi-universal repertoire of 20 canonical amino acids (AAs), numerous lines of evidence suggest that ancient proteins relied on a limited alphabet of 10 “early” AAs and that the 10 “late” AAs were products of biosynthetic pathways.
Reply:    Universal Genetic Code: The genetic code, which specifies the correspondence between codons (triplets of nucleotides) and amino acids, is nearly universal across all known life forms. If ancient proteins used a limited set of 10 amino acids, it would imply a different genetic code that would have had to evolve and replace the universal code found in all organisms today. This poses a significant challenge, as the genetic code is highly complex and there is no known plausible hypothesis how the code could have evolved. 

The genetic code, insurmountable problem for non-intelligent origin
https://reasonandscience.catsboard.com/t2363-the-genetic-code-insurmountable-problem-for-non-intelligent-origin

Eugene V. Koonin: Origin and evolution of the genetic code: the universal enigma 2012 Mar 5
In our opinion, despite extensive and, in many cases, elaborate attempts to model code optimization, ingenious theorizing along the lines of the coevolution theory, and considerable experimentation, very little definitive progress has been made. Summarizing the state of the art in the study of the code evolution, we cannot escape considerable skepticism. It seems that the two-pronged fundamental question: “why is the genetic code the way it is and how did it come to be?”, that was asked over 50 years ago, at the dawn of molecular biology, might remain pertinent even in another 50 years. Our consolation is that we cannot think of a more fundamental problem in biology.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293468/

Absence of Life Forms with 10 Amino Acids: As of our current knowledge, there are no extant life forms that operate with only 10 amino acids. All known organisms, from bacteria to humans, use a common set of 20 canonical amino acids in their protein synthesis. This suggests that the use of 20 amino acids in proteins is a fundamental feature of life rather than a later addition.

Essential Functions of Late Amino Acids: The 10 "late" amino acids, such as tryptophan, tyrosine, and histidine, have important roles in protein structure, enzymatic catalysis, and molecular recognition. These functions are crucial for the diverse range of biological processes observed in modern organisms. It would be challenging to account for the absence of these functions in ancient proteins if they were limited to only 10 amino acids.

Chemical Complexity: The diversity of chemical properties offered by the full set of 20 amino acids allows for a greater range of protein structures and functions. The inclusion of additional amino acids increases the repertoire of possible interactions and enhances the functional versatility of proteins. It is unlikely that such chemical complexity could arise solely through biosynthetic pathways without the need for additional amino acids.

No Direct Evidence: While there is evidence supporting the idea of a limited set of amino acids in ancient proteins, it is important to note that direct evidence from ancient proteins themselves is scarce. Fossilized proteins or genetic material from ancient organisms are challenging to obtain and study, making it difficult to draw definitive conclusions about the composition of ancient proteins.

Claim: However, many nonproteinogenic AAs were also prebiotically available, which begs two fundamental questions: Why do we have the current modern amino acid alphabet and would proteins be able to fold into globular structures as well if different amino acids comprised the genetic code? Here, we experimentally evaluate the solubility and secondary structure propensities of several prebiotically relevant amino acids in the context of synthetic combinatorial 25-mer peptide libraries. The most prebiotically abundant linear aliphatic and basic residues were incorporated along with or in place of other early amino acids to explore these alternative sequence spaces. The results show that foldability was likely a critical factor in the selection of the canonical alphabet. 
Reply:   Amino acid properties and interactions are determined by their inherent chemical and physical characteristics. Proteins and their folding patterns are the result of complex molecular interactions and forces, including hydrogen bonding, electrostatic interactions, hydrophobic effects, and van der Waals forces. The folding process is driven by the specific sequence of amino acids and their interactions with the surrounding environment. While certain amino acids may have properties that enhance foldability,  they would need to possess a  form of foresight or intentionality in terms future functional structural conformation.
The experimental evaluation of solubility and secondary structure propensities of prebiotically relevant amino acids does not necessarily provide definitive evidence for the selection of the modern amino acid alphabet. These experiments can shed light on the physical properties of amino acids and their potential role in protein folding, but they do not address the historical processes that led to the emergence of the modern amino acid repertoire.

Claim: Unbranched aliphatic amino acids were purged from the proteinogenic alphabet despite their high prebiotic abundance because they generate polypeptides that are oversolubilized and have low packing efficiency. Surprisingly, we find that the inclusion of a short-chain basic amino acid also decreases polypeptides’ secondary structure potential, for which we suggest a biophysical model. Our results support the view that, despite lacking basic residues, the early canonical alphabet was remarkably adaptive at supporting protein folding and explain why basic residues were only incorporated at a later stage of protein evolution.
Reply: The origin of the proteome to start life cannot be explained by evolution. Nor the selection of the first amino acid set.