ElShamah - Reason & Science: Defending ID and the Christian Worldview
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ElShamah - Reason & Science: Defending ID and the Christian Worldview

Welcome to my library—a curated collection of research and original arguments exploring why I believe Christianity, creationism, and Intelligent Design offer the most compelling explanations for our origins. Otangelo Grasso


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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?

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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?

https://reasonandscience.catsboard.com/t3084-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#8289

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

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? 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.

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? 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 ?!

https://reasonandscience.catsboard.com

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