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Defending the Christian Worlview, Creationism, and Intelligent Design

This is my personal virtual library, where i collect information, which leads in my view to the Christian faith, creationism, and Intelligent Design as the best explanation of the origin of the physical Universe, life, and biodiversity


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Defending the Christian Worlview, Creationism, and Intelligent Design » Origin of life » Amino Acids: Origin of the canonical twenty  amino acids required for life

Amino Acids: Origin of the canonical twenty  amino acids required for life

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Otangelo


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Amino acid synthesis requires solutions to four key biochemical problems

1. Nitrogen fixation
Nitrogen is an essential component of amino acids. Earth has an abundant supply of nitrogen, but it is primarily in the form of atmospheric nitrogen gas (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. Nitrogen in the form of ammonia is the source of nitrogen for all the amino acids. The carbon backbones come from the glycolytic pathway, the pentose phosphate pathway, or the citric acid cycle.


2. Selection of the 20 canonical bioactive amino acids
Why are 20 amino acids used to make proteins ( in some rare cases, 22) ?  Why not more or less ? And why especially the ones that are used amongst hundreds available? In a progression of the first papers published in 2006, which gave a rather shy or vague explanation, in 2017, the new findings are nothing short than astounding.  In January 2017, the paper : Frozen, but no accident – why the 20 standard amino acids were selected, reported:

" Amino acids were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets. Factors to take into account when assessing why a particular amino acid might be used include its component atoms, functional groups, biosynthetic cost, use in a protein core or on the surface, solubility and stability. Applying these criteria to the 20 standard amino acids, and considering some other simple alternatives that are not used, 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. Why the particular 20 amino acids were selected to be encoded by the Genetic Code remains a puzzle."

3. Homochirality
In amino acid production, we encounter an important problem in biosynthesis—namely, stereochemical control. Because all amino acids except glycine are chiral, biosynthetic pathways must generate the correct isomer with high fidelity. In each of the 19 pathways for the generation of chiral amino acids, the stereochemistry at the a -carbon atom is established by a transamination reaction that includes pyridoxal phosphate (PLP) by transaminase enzymes, which however were not extant on a prebiotic earth, which creates an unpenetrable origin of life problem. One of the greatest challenges of modern science is to understand the origin of the homochirality of life: why are most essential biological building blocks present in only one handedness, such as L-amino acids and D-sugars ?


4. Amino acid synthesis regulation
Biosynthetic pathways are often highly regulated such that building blocks are synthesized only when supplies are low. Very often, a high concentration of the final product of a pathway inhibits the activity of allosteric enzymes ( enzymes that use cofactors ) that function early in the pathway to control the committed step. These enzymes are similar in functional properties to aspartate transcarbamoylase and its regulators. Feedback and allosteric mechanisms ensure that all 20 amino acids are maintained in sufficient amounts for protein synthesis and other processes.

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Otangelo


Admin
Glycine: 
Phosphoglycerate dehydrogenase
http://en.wikipedia.org/wiki/Phosphoglycerate_dehydrogenase
Phosphoserine transaminase
http://en.wikipedia.org/wiki/Phosphoserine_transaminase
Phosphoserine phosphatase
http://en.wikipedia.org/wiki/Phosphoserine_phosphatase
Serine hydroxymethyltransferase
http://en.wikipedia.org/wiki/Serine_hydroxymethyltransferase

Valine
Acetolactate synthase enzyme
http://www.ebi.ac.uk/interpro/entry/IPR004789
Acetohydroxy acid isomeroreductase
http://www.ebi.ac.uk/interpro/entry/IPR013023
Dihydroxy-acid dehydratase
http://en.wikipedia.org/wiki/Dihydroxy-acid_dehydratase


Leucine and Isoleucine
Acetolactate synthase
https://en.wikipedia.org/wiki/Acetolactate_synthase
2-isopropylmalate synthase
https://en.wikipedia.org/wiki/2-isopropylmalate_synthase
3-Isopropylmalate dehydratase
https://en.wikipedia.org/wiki/3-Isopropylmalate_dehydratase
3-Isopropylmalate dehydrogenase
https://en.wikipedia.org/wiki/3-Isopropylmalate_dehydrogenase
Transaminase
https://en.wikipedia.org/wiki/Transaminase

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Otangelo


Admin
Tryptophan and the riddle of making amino acids by hypercomplex enzymatic reactions

https://reasonandscience.catsboard.com/t1740p25-amino-acids-origin-of-the-canonical-twenty-amino-acids-required-for-life#6700

If you can't make a brick, you can't make a house. Naturalistic scenarios are all based on ad-hoc anecdotal pseudo-scientific claims. Without having the right twenty left-handed amino acids,  life essential proteins cannot be made, nor protein complexes, nor biological cells. The pathway of tryptophan synthesis is perhaps the most thoroughly studied of any biosynthetic sequence, particularly in terms of its genetic organization and expression.

Never, in any simulated Origin of Life experiment, the amino acid Tryptophan was synthesized. Why? The biosynthesis pathway to make tryptophan is the most biochemically expensive and most complicated process of all life essential amino acid pathways, and tightly regulated. Glucose feeds the Glycolysis pathway, which utilizes nine enzymatic steps and enzymes to produce a subproduct, which enters the Shikimake pathway, which uses another seven enzymes, to make chorismate, which enters the Tryptophan biosynthesis pathway, and after another five steps and enzymes, finally produces Tryptophan. So, in total, 21 enzymes. 

Some enzymes in the pathway are highly sophisticated, veritable multienzyme nanomachines, like a paper called the bacterial tryptophan synthase, which channels the substrates through a long interconnecting tunnel with a clear logic: the substrate is not lost from the enzyme complex and diluted in the surrounding milieu. This phenomenon of direct transfer of enzyme-bound metabolic intermediates, or tunnelling, increases the efficiency of the overall pathway by preventing loss and dilution of the intermediate. Smart, hah ??!!

You can have a closer look at the entire pathway to make tryptophan here:
https://reasonandscience.catsboard.com/t1740-origin-of-the-canonical-twenty-amino-acids-required-for-life#5939

Now let me tell you why this is so relevant. Tryptophan is the substrate, used to make one of the most important electron carriers used in life: NAD:

Nicotinamide adenine dinucleotide (NAD) in origin of life scenarios
https://reasonandscience.catsboard.com/t2708-nicotinamide-adenine-dinucleotide-nad-in-origin-of-life-scenarios#6060

NAD is pivotal for cell life, first as a reusable redox coenzyme for energy production, second as a consumable substrate in enzymatic reactions regulating crucial biological processes, including gene expression, DNA repair, cell death and lifespan, calcium signaling, glucose homeostasis, and circadian rhythms.  (NADPH) is an essential electron donor in all organisms. It provides the reducing power that drives numerous anabolic reactions, including those responsible for the biosynthesis of all major cell components. It is also the driving force of most biosynthetic enzymatic reactions, including those responsible for the biosynthesis of all major cell components, such as DNA and lipids. The consumption of NADP+ is connected to the consumption of NAD+ and to the regulation of various major biological activities such as DNA repair, gene expression, apoptosis, nitrogen fixation, and calcium homeostasis.  (NADPH) is an essential electron donor in all organisms. It provides the reducing power that drives numerous anabolic reactions, including those responsible for the biosynthesis of all major cell components.


Free-living bacteria synthesize tryptophan (Trp), which is an essential amino acid for mammals, some plants, and lower eukaryotes. The Trp synthesis pathway appears to be highly conserved, and the enzymes needed to synthesize tryptophan are widely distributed across the three domains of life. This pathway is one of three that compose aromatic amino acids from chorismate.   As another point of distinction, the Trp pathway is the most biochemically expensive of the amino acid pathways, and for this reason, it is expected to be tightly regulated.   

Tryptophan (Trp) biosynthesis is a biologically expensive, complicated process. In fact, the products of four other pathways are essential contributors to carbon or nitrogen during tryptophan formation. Thus, the principal pathway precursor, chorismate, is also the precursor of the other aromatic amino acids, phenylalanine and tyrosine, as well as serving as the precursor of aminobenzoic acid and several other metabolites. 

Chorismate biosynthesis occurs via the shikimate pathway: 

1. DAHP synthase
2. 3-dehydroquinate synthase
3. 5-Dehydroquinate Synthetase
4. Shikimate dehydrogenase
5. Shikimate kinase
6. 3-enolpyruvylshikimate-5-phosphate synthase
7. Chorismate synthase

The Aromatic Amino Acids Are Synthesized from Chorismate
Indeed, chorismate is common to the synthesis of cellular compounds having benzene rings, including these amino acids, the fat-soluble vitamins E and K, folic acid, and coenzyme Q and plastoquinone (the two quinones necessary to electron transport during respiration and photosynthesis, respectively). Lignin, a polymer of nine-carbon aromatic units, is also a derivative of chorismate. Lignin and related compounds can account for as much as 35% of the dry weight of higher plants; clearly, enormous amounts of carbon pass through the chorismate biosynthetic pathway.

Enzymes and reactions in the Tryptophan biosynthesis pathway:
Tryptophan is synthesized in five steps from chorismate. Each step requires a specific enzyme activity. The four intermediates between chorismate and tryptophan serve no function other than as precursors of tryptophan.  

That means, these enzymes have no other purpose, and could not have been co-opted from other synthesis pathways. Their exclusive and necessity in intermediate stages make them irreducible, and the pathway as a whole is irreducibly complex. 

6. Anthranilate synthase
7. Anthranilate phosphoribosyltransferase
8. Phosphoribosylanthranilate isomerase
9. Indole-3-glycerol-phosphate synthase
10 + 11. Tryptophan synthase

Origin of Tryptophan biosynthesis and abiotic scenarios
Aromatic amino acid biosynthesis proceeds via a long series of reactions, most of them concerned with the formation of the aromatic ring before branching into the specific routes to phenylalanine, tyrosine, and tryptophan. Chorismate, the common intermediate of the three aromatic amino acids, is derived in eight steps from erythrose-4-phosphate and phosphoenolpyruvate.

How Structure Arose in the Primordial Soup
Tryptophan, in comparison, has a complex structure and is comparatively rare in the protein code, like a Y or Z, leading scientists to theorize that it was one of the latest additions to the code. 6

How Structure Arose in the Primordial Soup
May 19, 2015
In research published online in March in the Journal of Molecular Evolution, Fournier showed that the last chemical letter added to the code was a molecule called tryptophan 2

Ancestral Reconstruction of a Pre-LUCA Aminoacyl-tRNA Synthetase Ancestor Supports the Late Addition of Trp to the Genetic Code.1 
2015 Mar 20
The genetic code was likely complete in its current form by the time of the last universal common ancestor (LUCA). Several scenarios have been proposed for explaining the code’s pre-LUCA emergence and expansion, and the relative order of the appearance of amino acids used in translation. One co-evolutionary model of genetic code expansion proposes that at least some amino acids were added to the code by the ancient divergence of aminoacyl-tRNA synthetase (aaRS) families. 

It is important to remark that secular science puts the origin and appearance of amino acids prior to LUCA. That said, it's clear that any allusion to evolution is prohibited by the fact that there was no evolution prior to DNA replication.

1. https://www.ncbi.nlm.nih.gov/pubmed/25791872
2. https://www.scientificamerican.com/article/how-structure-arose-in-the-primordial-soup/
3. http://2009.igem.org/wiki/images/a/a7/The_tryptophan_biosynthetic_pathway.pdf
4. http://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/18486479
5. Origins of Life on the Earth and in the Cosmos SECOND EDITION, page 117
6. https://www.scientificamerican.com/article/how-structure-arose-in-the-primordial-soup/
7. https://www.nature.com/scitable/topicpage/an-evolutionary-perspective-on-amino-acids-14568445
8. https://en.wikipedia.org/wiki/Tryptophan

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29Amino Acids: Origin of the canonical twenty  amino acids required for life - Page 2 Empty Tryptophan Thu Feb 06, 2020 12:47 pm

Otangelo


Admin
Tryptophan

Enzymes and reactions in the Tryptophan biosynthesis pathway:

Tryptophan is synthesized in five steps from chorismate. Each step requires a specific enzyme activity. The four intermediates between chorismate and tryptophan serve no function other than as precursors of tryptophan. these enzymes have no other purpose, and could not have been co-opted from other synthesis pathways. Their exclusive and necessity in intermediate stages make them irreducible, and the pathway as a whole is irreducibly complex.Enzymes and reactions in the Tryptophan biosynthesis pathway:

1. DAHP synthase
2. 3-dehydroquinate synthase
3. 5-Dehydroquinate Synthetase
4. Shikimate dehydrogenase
5. Shikimate kinase
6. 3-enolpyruvylshikimate-5-phosphate synthase
7. Chorismate synthase8. Anthranilate synthase
9. Anthranilate phosphoribosyltransferase
10. Phosphoribosylanthranilate isomerase
11. Indole-3-glycerol-phosphate synthase
12 + 11. Tryptophan synthase

The bacterial tryptophan synthases are multienzyme nanomachines that catalyze the last two steps in L-tryptophan biosynthesis. 4

Aromatic amino acid biosynthesis proceeds via a long series of reactions, most of them concerned with the formation of the aromatic ring before branching into the specific routes to phenylalanine, tyrosine, and tryptophan. Chorismate, the common intermediate of the three aromatic amino acids, is derived in eight steps from erythrose-4-phosphate and phosphoenolpyruvate.

It is important to remark that secular science puts the origin and appearance of amino acids prior to LUCA. That said, it's clear that any allusion to evolution is prohibited by the fact that there was no evolution prior to DNA replication.

1. https://www.ncbi.nlm.nih.gov/pubmed/25791872
2. https://www.scientificamerican.com/article/how-structure-arose-in-the-primordial-soup/
3. http://2009.igem.org/wiki/images/a/a7/The_tryptophan_biosynthetic_pathway.pdf
4. http://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/18486479
5. Origins of Life on the Earth and in the Cosmos SECOND EDITION, page 117
6. https://www.scientificamerican.com/article/how-structure-arose-in-the-primordial-soup/
7. https://www.nature.com/scitable/topicpage/an-evolutionary-perspective-on-amino-acids-14568445
8. https://en.wikipedia.org/wiki/Tryptophan

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Otangelo


Admin
Scientists find biology's optimal 'molecular alphabet' may be preordained

https://phys.org/news/2019-09-scientists-biology-optimal-molecular-alphabet.html?fbclid=IwAR18uckj_nrJ1p6B8Gi7n3QRW-WoAnEi3RH57SrOXxoj6yvjx5CkofkWqAY

There are millions of possible types of amino acids that could be found on Earth or elsewhere in the universe, each with its own distinctive chemical properties. Indeed, scientists have found these unique chemical properties are what give biological proteins, the large molecules that do much of life's catalysis, their own unique capabilities. The team had previously measured how the CAA set compares to random sets of amino acids and found that only about 1 in a billion random sets had chemical properties as unusually distributed as those of the CAAs.

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Otangelo


Admin
Dimas A. M. Zaia A Few Experimental Suggestions Using Minerals to Obtain Peptides with a High Concentration of L-Amino Acids and Protein Amino Acids 10 December 2020

The peptides/proteins of all living beings on our planet are mostly made up of 19 L-amino acids and glycine, an achiral amino acid. Arising from endogenous and exogenous sources, the seas of the prebiotic Earth could have contained a huge diversity of biomolecules (including amino acids), and precursors of biomolecules. 

My comment: Agreed. There is NO REASON or function whatsoever that molecules could have benefitted from, by performing a selection of amino acids used in life.

Thus, how were these amino acids selected from the huge number of available amino acids and other molecules? What were the peptides of prebiotic Earth made up of? How were these peptides synthesized? Minerals have been considered for this task, since they can preconcentrate amino acids from dilute solutions, catalyze their polymerization, and even make the chiral selection of them.

My comment: How could mineral select the chiral form of amino acids? I have never seen a science paper solving that issue. 

However, until now, this problem has only been studied in compartmentalized experiments. There are separate experiments showing that minerals preconcentrate amino acids by adsorption or catalyze their polymerization

My comment: The polymerization would/could have occurred by binding one amino acid to another at any of the possible binding sites, like on the side chain.

or separate L-amino acids from D-amino acids. Based on the [GADV]-protein world hypothesis, as well as the relative abundance of amino acids on prebiotic Earth obtained by Zaia, several experiments are suggested. The main goal of these experiments is to show that using minerals it is possible, at least, to obtain peptides whose composition includes a high quantity of L-amino acids and protein amino acids (PAAs). These experiments should be performed using hydrothermal environments and wet/dry cycles. In addition, for hydrothermal environment experiments, it is very important to use one of the suggested artificial seawaters, and for wet/dry environments, it is important to perform the experiments in distilled water and diluted salt solutions.

My comment: The only problem is that distilled water was not the medium in the prebiotic earth....

Finally, from these experiments, we suggest that, without an RNA world or even a pre genetic world, a small peptide set could emerge that better resembles modern proteins.

https://www.mdpi.com/2073-8994/12/12/2046

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Otangelo


Admin
Why are 20 amino acids used to make proteins? Why not more or less ? And why especially the ones that are used amongst hundreds available?
Science is absolutely clueless about how the optimal set of amino acids to make proteins emerged. Francis Crick attributed  the formation of the genetic code to an example of a frozen accident.  According to this hypothesis, the genetic code was formed through a random, highly improbable combination of its components formed by an abiotic route. Besides the problem to explain the origin of the genetic code, about which Eugene Koonin wrote: " we cannot think of a more fundamental problem in biology ", there is another, not less enigmatic situation : Why are 20 amino acids used to make proteins ( in some rare cases, 22) ?  Why not more or less ? And why especially the ones that are used amongst hundreds available? 

The study's experiment points to chemical evolution having prefabricated some amino acid chains useful in living systems before life had evolved a way to make proteins. The preference for the incorporation of the biological amino acids over non-biological counterparts also adds to possible explanations for why life selected for just 20 amino acids when 500 occurred naturally on the Hadean Earth. 14

In a progression of the first papers published in 2006, which gave a rather shy or vague explanation, in 2017, the new findings are nothing short than astounding.  In January 2017, the paper : Frozen, but no accident – why the 20 standard amino acids were selected, reported:

" Amino acids were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets. Factors to take into account when assessing why a particular amino acid might be used include its component atoms, functional groups, biosynthetic cost, use in a protein core or on the surface, solubility and stability. Applying these criteria to the 20 standard amino acids, and considering some other simple alternatives that are not used, 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. Why the particular 20 amino acids were selected to be encoded by the Genetic Code remains a puzzle." 

It remains a puzzle as so many other things in biology which find no answer when answers are constraint to a set of possible explanations, where an intelligent causal agency is excluded a priori. Only intelligence actively selects. Attributes, that unguided, random events lacks and is too unspecific,  but an intelligent creator can employ to create life. The authors also write about natural selection and evolution, a mechanism that has no place to explain the origin of life.

The paper continues: 
" Here, I argue that there are excellent reasons for using (or not using) each possible amino acid and that the set used is near optimal.
Biosynthetic cost
Protein synthesis takes a major share of the energy resources of a cell. Table 1 shows the cost of biosynthesis of each amino acid, measured in terms of number of glucose and ATP molecules required. These data are often nonintuitive. For example, Leu costs only 1 ATP, but its isomer Ile costs 11. Why would life ever, therefore, use Ile instead of Leu, if they have the same properties? Larger is not necessarily more expensive; Asn and Asp cost more in ATP than their larger alternatives Gln and Glu, and large Tyr cost only two ATP, compared to 15 for small Cys. The high cost of sulfur-containing amino acids is notable. " 

This is indeed completely counterintuitive and does not conform with naturalistic predictions.

" Burial and surface
Proteins have close-packed cores with the same density as organic solids and side chains fixed into a single conformation. A solid core is essential to stabilize proteins and to form a rigid structure with well-defined binding sites. Nonpolar side chains have therefore been selected to stabilize close-packed hydrophobic cores. Conversely, proteins are dissolved in water, so other side chains are used on a protein surface to keep them soluble in an aqueous environment. " 

The problem here is that molecules and an arrangement of correctly selected variety of amino acids would bear no function until life began. Functional subunits of proteins, or even fully operating proteins by their own would only have function, after life began, and the cells intrinsic operations were on the go. It is as if molecules had the inherent drive to contribute to life to have the first go, which of course is absurd. The only rational alternative is that a powerful creative agent had foresight, and new which arrangement and selection of amino acids would fit and work to make life possible.

"Which amino acids came first?
It is plausible that the first proteins used a subset of the 20 and a simplified Genetic Code, with the first amino acids acquired from the environment." 

Why is plausible? It is not only not plausible, but plain and clearly impossible. The genetic code could not emerge gradually, and there is no known explanation how it emerged. The author also ignores that the whole process of protein synthesis requires all parts of the process fully operational right from the beginning. A gradual development by evolutionary selective forces is impossible.

" Energetics of protein folding
Folded proteins are stabilized by hydrogen bonding, removal of nonpolar groups from water (hydrophobic effect), van der Waals forces, salt bridges and disulfide bonds. Folding is opposed by loss of conformational entropy, where rotation around bonds is restricted, and introduction of strain. These forces are well balanced so that the overall free energy changes for all the steps in protein folding are close to zero." 

Foresight and superior knowledge would be required to know how to get a protein fold that bears function, and where the forces are outbalanced naturally to get an overall energy homeostatic state close to zero.

" Conclusion
There are excellent reasons for the choice of every one of the 20 amino acids and the nonuse of other apparently simple alternatives. If all else fails, one can resort to chance or a ‘frozen accident’, as an explanation. " 

Or to design ?!



A quantitative investigation of the chemical space surrounding amino acid alphabet formation 9
21 January 2008
To date, explanations for the origin and emergence of the alphabet of amino acids encoded by the standard genetic code have been largely qualitative and speculative. Here, with the help of computational chemistry, we present the first quantitative exploration of nature’s ‘‘choices’’ set against various models for plausible alternatives. Specifically, we consider the chemical space defined by three fundamental biophysical properties (size, charge, and hydrophobicity) to ask whether the amino acids that entered the genetic code exhibit a higher diversity than random samples of similar size drawn from several different definitions of amino acid possibility space. In summary, the question of whether early life selected a non-randomly diverse alphabet of amino acids remains far from clear in this initial inquiry into the chemical space of prebiotic amino acids.

Did Evolution Select a Nonrandom ‘‘Alphabet’’ of Amino Acids? 2
26 January 2011
The last universal common ancestor of contemporary biology (LUCA) used a precise set of 20 amino acids as a standard alphabet with which to build genetically encoded protein polymers. Considerable evidence indicates that some of these amino acids were present through nonbiological syntheses prior to the origin of life, while the rest evolved as inventions of early metabolism.

Invention indicates teleology, which there is no justification to bring it into the game. There could also not yet have been evolutionary forces at work since evolution depends on a full setup and extant proteome, which origin is what is being tried to be elucidated.  

One possibility is that natural selection favored a set of amino acids that exhibits clear, nonrandom properties—a set of especially useful building blocks.

So did lifeless matter have the goal to become useful? Useful for what ? for life? So did lifeless matter have the inherent drive to group and transform itself to form building blocks , later used to make molecular machines, that would drive life?

Calculating the expected characteristics for a random alphabet of amino acids
Building from these assumptions, we performed three specific tests: we compared (in terms of coverage) (i) the full set of 20 genetically encoded amino acids for size, charge, and hydrophobicity with equivalent values calculated for a sample of 1 million alternative sets (each also comprising 20 members) drawn randomly from the pool of 50 plausible prebiotic candidates

Conclusions:
we see a consistent, unambiguous pattern; random chance would be highly unlikely to represent the chemical space of possible amino acids with such breadth and evenness in charge, size, and hydrophobicity (properties that define what protein structures and functions can be built).

MAPPING AMINO ACIDS TO UNDERSTAND LIFE'S ORIGINS 7
Jan 13, 2014
Only 20 standard amino acids are used to build proteins, but why exactly nature "chose" these particular amino acids is still a mystery. One step towards solving this is to explore the “amino acid space”, the set of possible or hypothetical amino acids that might have been used instead.

Cartography of amino acids
The number of amino acid structures generated surpasses all previous estimates. Using the method with the single fuzzy formula produced 120,000 plausible structures and using ten fuzzy formulas narrows this down to a more biologically relevant set of nearly 4,000 amino acids. This shows that there were a staggering amount of options available that could have possibly been used for building the genetically encoded amino acid set – and yet there are only 20. They compared the output of both methods to databases of biological alpha amino acids beyond the 20 genetic ones, as well as to amino acids found in carbonaceous meteorites.

Beyond Terrestrial Biology: Charting the Chemical Universe of α‑Amino Acid Structures 8
October 23, 2013
Nonbiological processes can and often do produce far more than 20 amino acids, including α-amino acids beyond those found in the genetic code, as well as β-, γ-, and δ-amino acids and others

Amino Acids: Origin of the canonical twenty  amino acids required for life - Page 2 LR4UdVa
Generic structural types of amino acids, shown as their zwitterions with respect to their core α-amino acid motif, using standard notation that R is a side chain of variable structure and composition: 
(Ia) and (Ib) are the L- and D-stereoisomers of a simple α-amino acid; (Ic) is an α,α-dialkyl amino acid with two alkyl side chains bound to the α carbon; (IIa) and (IIb) show two of the many variations that become possible when an extra carbon atom is inserted between amino and carboxyl functional groups so as to form a β-amino acid; (III) is a γ-amino acid; (IVa), (IVb), and (IVc) illustrate secondary, tertiary, and quaternary amines, respectively. All genetically encoded amino acids are of type (Ia) with the exception of proline, which is of type (IVa).

75 to 100 different amino acids have been detected in the Murchison meteorite to date, and improvements in analytical sensitivity continue to reveal a far greater diversity of molecular structure than was previously suspected in both meteoritic samples and prebiotic simulations. Despite this molecular diversity, the products of abiotic chemistry can account for only around half of the 20 genetically encoded amino acids. The amino acids selenocysteine and pyrrolysine, which fit this description, are currently entering the genetic code as the 21st and 22nd coded amino acid within some lineages. In this context, it is noteworthy that diverse biological systems use far more types of amino acids than the 20 into which genes are decoded. These additional amino acids fall into various categories, including secondary metabolites, post-translational modifications, amino acids used in nonribosomal peptide synthesis, and intermediates of the metabolic pathways by which the standard 20 are synthesized and degraded. The total number of amino acids occurring in biological systems is unknown; however, estimates range into the hundreds or thousands, with the majority found in plants and microbes.

Since abiotic synthesis and metabolism can each produce many amino acids besides those found in the genetic code,  20 for use in genetic coding were selected from a much larger pool of possible chemical structures. While simple algorithms have been used to calculate the total number of possible alkyl amino acids, the incorporation of heteroatoms (i.e., atoms other than carbon or hydrogen) vastly increases the potential for molecular diversity and the corresponding challenges for exploration. An important challenge here is to understand whether physical or chemical principles predict which 20 α-amino acids would be selected  from the near-infinite number of structural possibilities. Are other possible combinations better in some obvious functional respects, such as in the coverage of physical properties which might be useful in protein folding or catalysis? If so, then the outcome  may represent some degree of ″frozen accident″, as has been advanced for other aspects of the genetic code.

Does Life Use a Non-Random Set of Amino Acids? 1
Biology could conceivably have used a different amino acid alphabet, and there appears to be a fairly wide range from which it could have chosen. But is there anything special — is there anything unique or unusual — about the set of 20 amino acids (some organisms use one or two additional amino acids) that life does use? And, if there is, how might this fundamentally non-random contingency be explained?

Jonathan M. of Evolutionnews comments: 
If chance and necessity are seemingly inadequate, either on their own or in co-operation, what about the causal powers of agent causality? Such delicately balanced and finely-tuned parameters are routinely associated with purposive agents. Agents are uniquely endowed with the capacity of foresight, and have the capacity to visualise and subsequently actualise a complex and finely-tuned information-rich system, otherwise unattainable by chance and law. If, in every other realm of experience, such features are routinely attributed to intelligent causes, and we have seen no reason to think that this intuition is mistaken, are we not justified in positing and inferring that these systems we are finding in biology also originated at the will of a purposive conscious agent?

Paper Reports that Amino Acids Used by Life Are Finely Tuned to Explore “Chemistry Space” 3
June 5, 2015
A recent paper in Nature‘s journal Scientific Reports, “Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids,” has found that the twenty amino acids used by life are finely tuned to explore “chemistry space” and allow for maximal chemical reactions. Considering that this is a technical paper, they give an uncommonly lucid and concise explanation of what they did:

Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids 4
24 March 2015
We drew 10^8 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 10^8 possibilities tested.

Luskin of Evolutionnews continues: 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.

Nature continues: This is consistent with the hypothesis that natural selection influenced the composition of the encoded amino acid alphabet, contributing one more clue to the much deeper and wider debate regarding the roles of chance versus predictability in the evolution of life.

Amino Acids: Origin of the canonical twenty  amino acids required for life - Page 2 WHgxPWR
The number of random sets (out of 10^8, or 100,000,000) with better coverage than the encoded amino acids in one, two, or three properties. 
Note that the circles are not drawn to scale; an appropriately scaled circle representing the number of random sets with better coverage in all three properties than the encoded set would only cover an area approximately 1/ 100th of that of the period at the end of this sentence.

Well, or maybe there was neither evolution, nor natural selection, and if chance is not a good explanatory candidate, we might consider another option, commonly ignored by secular science: Selection by an intelligent agency with foresight and higher intelligence.

Frozen, but no accident – why the 20 standard amino acids were selected 6
13 January 2017
The 20 standard amino acids encoded by the Genetic Code were adopted during the RNA World, around 4 billion years ago. This amino acid set could be regarded as a frozen accident, implying that other possible structures could equally well have been chosen to use in proteins. Amino acids were not primarily selected for their ability to support catalysis, as the RNA World already had highly effective cofactors to perform reactions, such as oxidation, reduction and transfer of small molecules. Rather, they were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets. Factors to take into account when assessing why a particular amino acid might be used include its component atoms, functional groups, biosynthetic cost, use in a protein core or on the surface, solubility and stability. Applying these criteria to the 20 standard amino acids, and considering some other simple alternatives that are not used, 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.

Setting the common a priori mainstream science assumptions aside, the last sentence is remarkable. " the set of amino acids selected appears to be near ideal. ". 

Andrew J.Doing ( author of the paper ): Why the particular 20 amino acids were selected to be encoded by the Genetic Code remains a puzzle.

It remains a puzzle as so many other things in biology which find no answer by the ones that build their inferences on a constraint set of possible explanations, where an intelligent causal agency is excluded a priori. Selection is an active process, that requires intelligence. Attributes, that chance alone lacks, but an intelligent creator can employ to create life. The authors also write about natural selection and evolution, a mechanism that has no place to explain the origin of life. 

Here, I argue that there are excellent reasons for using (or not using) each possible amino acid and that the set used is near optimal.

Biosynthetic cost
Protein synthesis takes a major share of the energy resources of a cell [12]. Table 1 shows the cost of biosynthesis of each amino acid, measured in terms of number of glucose and ATP molecules required. These data are often nonintuitive. For example, Leu costs only 1 ATP, but its isomer Ile costs 11. Why would life ever therefore use Ile instead of Leu, if they have the same properties? Larger is not necessarily more expensive; Asn and Asp cost more in ATP than their larger alternatives Gln and Glu, and large Tyr costs only two ATP, compared to 15 for small Cys. The high cost of sulfur-containing amino acids is notable.

This is indeed completely counterintuitive and does not conform with naturalistic predictions.

Burial and surface
Proteins have close-packed cores with the same density as organic solids and side chains fixed into a single conformation. A solid core is essential to stabilise proteins and to form a rigid structure with well-defined binding sites. Nonpolar side chains have therefore been selected to stabilise close-packed hydrophobic cores. Conversely, proteins are dissolved in water, so other side chains are used on a protein surface to keep them soluble in an aqueous environment.

The problem here is that molecules and an arrangement of correctly selected variety of amino acids would bear no function until life began. Functional subunits of proteins, or even fully operating proteins by their own would only have function, after life began, and the cells intrinsic operations were on the go. It is as if molecules had the inherent drive to contribute to life to have a first go, which of course is absurd. The only rational alternative is that a powerful creator had foresight, and new which arrangement and selection of amino acids would fit and work to make life possible.

Which amino acids came first?
It is plausible that the first proteins used a subset of the 20 and a simplified Genetic Code, with the first amino acids acquired from the environment.

Why is plausible? It is not only not plausible, but plain and clearly impossible. The genetic code could not emerge gradually, and there is no known explanation how it emerged. The author also ignores that the whole process of protein synthesis requires all parts in the process fully operational right from the beginning. A gradual development by evolutionary selective forces is impossible.

Energetics of protein folding
Folded proteins are stabilised by hydrogen bonding, removal of nonpolar groups from water (hydrophobic effect), van der Waals forces, salt bridges and disulfide bonds. Folding is opposed by loss of conformational entropy, where rotation around bonds is restricted, and introduction of strain. These forces are well balanced, so that the overall free energy changes for all the steps in protein folding are close to zero.

Foresight and superior knowledge would be required to know how to get a protein fold that bears function, and where the forces are outbalanced naturally to get an overall energy homeostatic state close to zero.

Conclusion
There are excellent reasons for the choice of every one of the 20 amino acids and the nonuse of other apparently simple alternatives. If all else fails, one can resort to chance or a ‘frozen accident’, as an explanation.

Or to design ?!


The 20 standard amino acids - as general reasons for choosing side chains, we can now consider the 20 individually.


Side chain negative
• Aspartic acid - Asp - D 
• Glutamic acid - Glu - E 


Aspartic, Glutamic acid

The carboxyl group is stable, has a negative charge for strong electrostatic bonds, binds metals, is an excellent hydrogen bond acceptor, increases protein solubility and can transfer protons. Its twofold symmetry means that the entropic cost of fixing the carboxyl group is low.As Asp and Glu (and Asn and Gln) have the same functional groups, why do we have two pairs of these amino acids? At some sites, Asp and Glu (or Asn and Gln) can readily substitute for each other. However, this is not always the case. The first residue preceding the α-helix is the N-cap; Asp and Asn are strongly favoured here as they can accept hydrogen bonds from free backbone NH groups. Glu and Gln cannot do this, as their extra CH2 group pushes their functional groups out beyond the helix terminus. Similarly, at the second (N2) position of an α-helix, Gln and Glu are frequently found because they can loop around and hydrogen bond to the backbone NH groups. Asn and Asp are too short to form these rings. Glu to Asp or Gln to Asn can sometimes thus be very nonconservative substitutions, so all four are used.

Lysine, Arginine

Lys and Arg are used to give a protein solubility and for catalysis. They are rarely buried, not only because they have positively charged groups, but also because they are on the ends of long, flexible, straight chains, with four rotatable bonds. Their functional groups are also valuable when a positive charge is needed. Arg, in particular, is a superb hydrogen bond donor, with five NH bonds, polarised due to its delocalised positive charge.
Nonpolar residues, such as Leu and Ile, are also often found on the protein surface. One might expect this to be a problem for the protein, as they will reduce protein solubility. If there are Lys or Arg side chains nearby, however, nonpolar groups can form hydrophobic interactions with the CH2 groups in the Lys and Arg side chains. Nonpolar side chains would thus be less tolerated on the surface if charged groups had fewer CH2 groups.

Side chain positive
• Arginine - Arg - R 
• Lysine - Lys - K 

• Histidine - His - H 

Histidine

While the range of chemical reactions available to the 20 side chains is dismally poor, they are good at proton transfer. Rates of proton transfer are maximised when the general acid has a pKa that is the same as the environment. His, with a pKa of around 6.5, is easily tweaked by varying its environment, is an excellent side chain for general acid and base catalysis and is thus abundantly found in active sites requiring proton transfer. It is also often found binding metals.

[size=13]Lysine, Arginine[/size]

Lys and Arg are used to give a protein solubility and for catalysis. They are rarely buried, not only because they have positively charged groups, but also because they are on the ends of long, flexible, straight chains, with four rotatable bonds. Their functional groups are also valuable when a positive charge is needed. Arg, in particular, is a superb hydrogen bond donor, with five NH bonds, polarised due to its delocalised positive charge.
Nonpolar residues, such as Leu and Ile, are also often found on the protein surface. One might expect this to be a problem for the protein, as they will reduce protein solubility. If there are Lys or Arg side chains nearby, however, nonpolar groups can form hydrophobic interactions with the CH2 groups in the Lys and Arg side chains. Nonpolar side chains would thus be less tolerated on the surface if charged groups had fewer CH2 groups.

Uncharged polar (usually participate in hydrogen bonds as proton donors or acceptors):
• Glutamine - Gln - Q 
• Asparagine - Asn - N 
• Serine - Ser - S 
• Threonine - Thr - T 
• Tyrosine - Tyr - Y 


Serine, Threonine, Asparagine, Glutamine, Tyrosine
These amino acids frequently hydrogen bond to other side chains, amide groups in the backbone, to substrates or to ligands. The intrinsic benefit of hydrogen bond formation is offset by the conformational entropic cost of fixing the side chain in position and strain. Functional groups selected for hydrogen bonding are thus on the ends of short chains, with just one or two CH2 groups, so that the cost of restricting them is low and their biosynthetic cost is minimised.The aromatic ring in Tyr lowers the pKa of its OH, making it easier to form an O− group and act as an acid. Tyr can also form functional radicals, such as in ribonucleotide reductase, photosystem II and prostaglandin H synthase and transport electrons in pili.Allothreonine, with the opposite chirality at its Cβ, decomposes twice as fast, so threonine may have been selected for this reason.

Hydrophobic (normally buried inside the protein core):

Side chain nonpolar
• Alanine - Ala - A 
• Isoleucine - Ile - I 
• Leucine - Leu - L 
• Methionine - Met - M 
• Phenylalanine - Phe - F 
• Valine - Val - V 
• Proline - Pro - P 
• Glycine - Gly - G

• Cysteine - Cys - C 
• Tryptophan - Trp - W

Alanine

Ala is small and cheap. Its CH3 side chain has little surface to form van der Waals bonds, but it has a profound effect on the backbone, restricting it to either the α- or β-conformations. It is therefore more energetically favourable to put Ala into secondary structure than Gly. The formation of an isolated α-helix in water restricts rotations in side chains in all amino acids, except Ala and Gly. Hence, Ala has the highest preference to be in isolated α-helices .

Valine, Leucine, Isoleucine, Phenylalaline

These hydrocarbon side chains are clearly present to drive protein folding by forming hydrophobic cores, yet why exactly these were selected deserves an explanation. Firstly, why are there so many hydrocarbon side chains, rather than just, say, Leu? Multiple hydrocarbon side chains may be used as they are required to fill a protein core with no clashes and no holes. A variety of pieces are required to fit all the gaps within a protein core. Each can adopt a number of rotamers with similar energies , thus giving a range of possible shapes for each side chain. Thus, Leu and Ile are both needed to increase the range of possible hydrocarbon 3D shapes, despite Ile being more costly to synthesise . Val, Leu, Ile and Phe are striking in that they all have branched carbons, rather than straight chains. Using a branch gives one fewer dihedral angle to be fixed compared to a straight chain. Side chains therefore enter a protein core not just because they are hydrophobic, but also because they do not lose too much conformational entropy when they fold. Similarly, rings are rigid, so Phe has a large hydrocarbon surface and only two bonds to be fixed. Hydrocarbon side chains larger than Phe, Ile or Leu may not be used, as they would be less soluble as amino acids. A cyclohexane ring is also less soluble than a benzene ring, so Phe is used, rather than cyclohexylalanine.
Ile and Thr differ from the other 18 in that they have centres of chirality in their side chains. Alloisoleucine has the opposite chirality at its Cβ. The selection of isoleucine over alloisoleucine seems to be chance.

Methione

The explanation above for why branched side chains are preferred over straight chains fails for Met. Met has three bonds to be fixed if it is used in a protein core, giving less stabilisation than one might expect for its size. The first use of Met in protein is likely not to have been for protein stability, however, but rather for initiation of protein synthesis, using the AUG codon and formylMet. Occasional use of AUG would then allow Met to be found at other sites in a protein, such as in forming sulfur–aromatic interactions. It may also be useful in forming a hydrophobic core with its unique shape. Met is prone to oxidation at its sulfur, potentially leading to loss of protein function, but this would not have occurred before the Great Oxidation Event around 2.3 billion years. Met is also the most expensive amino acid to biosynthesise. Life is now stuck with this nonideal amino acid.

Cysteine

A key function of proteins is to bind metals. Soft metals, such as copper, zinc and cadmium, bind more tightly to sulfur than to oxygen. Cys may therefore have been selected for its metal binding properties, despite its high biosynthetic cost. In particular, Cys is commonly used to bind iron-sulfur clusters. These cofactors are found in a wide variety of metalloproteins, are playing crucial roles in metabolism and are very ancient. The SH side chain is also an effective nucleophile; it has a lower pKa than OH, readily forming S−.
Cys is the only side chain able to perform redox reactions, by forming disulfide bonds to stabilise folded proteins. Cys was selected in an anaerobic environment, however, where disulfide bond formation would have been rare or nonexistent. It is therefore not plausible that Cys was selected for its ability to form disulfides, and its subsequent use for this purpose, starting very approximately 1.5 billion years later after the Great Oxidation Event, is a lucky accident.

Maybe neither the atmosphere was anaerobic, and neither was it a lucky accident that Cys was selected.  

Proline

The unique structure of Pro, with no backbone NH group and its ring restricting its backbone, means that it is incompatible with many sites in a protein. Nevertheless, it can be highly stabilising, if its ring locks it into a desired conformation, such as within turns. Indeed, it has the lowest conformational entropic cost of folding of any amino acid. Pro is the simplest stable ring structure linking the Cα and N in an amino acid.

Tryptophan

Trp with its double aromatic ring is the least abundant amino acid and the most expensive to synthesise. It has some distinct properties: Trp, with an absorption maximum at around 280 nm, is well suited to be a UV-B chromophore The UVR8 protein uses an excitonically coupled Trp pyramid for this purpose in plants, for example, detecting potentially damaging levels of UV radiation. The Trp indole chromophore may therefore have been selected to help protect organisms from the intense UV radiation that was present on early Earth in the absence of an ozone layer.

Transition from prebiotic amino acid synthesis, to biosynthesis pathways in modern cells to synthesize amino acids

Little information in peer-reviewed scientific papers can be found to answer this key question: How could a supposed transition from prebiotic synthesis of amino acids, to the extremely complex biosynthesis pathways in modern cells have occurred? The sobering answer is: there are no answers. There is a huge unbridgeable gap. Following science paper describes the dilemma as follows:

On the Development Towards the Modern World: A Plausible Role of Uncoded Peptides in the RNA World 5
2009
Arguably one of the most outstanding problems in understanding the progress of early life is the transition from the RNA world to the modern protein based world. One of the main requirements of this transition is the emergence of mechanism to produce functionally meaningful peptides and later, proteins. What could have served as the driving force for the production of peptides and what would have been their properties and purpose in the RNA world? The answer may seem immediately clear; proteins are better enzymes than ribozymes.

The unwarranted insertion of teleology is implicitly clear and demonstrates the easy insertion of pseudo-explanations which do no justice and are inadequate to explain the monstrous problem that origin of life researchers face: Let's say it loud and clear. Unanimated matter does not select goal-oriented, what better works. Better for what ? for cellular functions? that's certainly true, but: do molecules have foresight or goals?  

However, modern proteins are only useful in their folded stated, whereas peptides need to reach a critical size and specific amino acid sequence before they fold into a functional biomolecules. It is more than likely that emerging peptides were not immediately useful as operational enzymes.

Then, why would they emerge AT ALL? 

Herein we describe two plausible roles that emerging peptides could have played, firstly support of the pre-existing RNA machinery. 

Based on what evidence do the authors suppose there was a pre-existing RNA machinery in place ? that are simply unwarranted made up assertions and scenarios. 

and secondly as early chemical catalysts. During the era of the RNA world, protein (or peptide) evolution would have been strongly coupled to the extant RNA infrastructure development.

There was no evolution at this stage. 

Thus, the emergence of peptides as a mechanism for supporting pre-existing RNA machinery, is a sound reason for peptides to be retained in an RNA world.

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