ElShamah - Reason & Science: Defending ID and the Christian Worldview
Would you like to react to this message? Create an account in a few clicks or log in to continue.
ElShamah - Reason & Science: Defending ID and the Christian Worldview

Otangelo Grasso: This is my library, where I collect information and present arguments developed by myself that lead, in my view, to the Christian faith, creationism, and Intelligent Design as the best explanation for the origin of the physical world.

You are not connected. Please login or register

Amyloid's, and origin of life scenarios

Go down  Message [Page 1 of 1]

1Amyloid's, and origin of life scenarios Empty Amyloid's, and origin of life scenarios Tue May 23, 2023 12:52 pm



Amyloids, and Origin of life scenarios

What are amyloids?

Amyloids are insoluble protein aggregates characterized by a specific cross-β-sheet structure. They form when normally soluble proteins misfold and aggregate into fibrils, which have a distinct morphology and biochemical properties. Amyloid fibrils are elongated structures composed of protein monomers arranged in a cross-β-sheet conformation, where the β-strands run perpendicular to the fibril axis and form a characteristic spine.

The aggregation process involves a series of steps, starting from the misfolding of soluble proteins into oligomers, which then assemble into protofibrils. These protofibrils further undergo structural reorganization and elongation to form mature amyloid fibrils. The fibrils are often resistant to degradation and can accumulate in tissues, leading to the formation of plaques or deposits.

Amyloids are associated with several diseases, including neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases, as well as non-neurological conditions like type 2 diabetes and certain forms of systemic amyloidosis. In these diseases, specific proteins or peptides adopt abnormal conformations and self-assemble into amyloid structures, which can disrupt normal cellular functions and contribute to tissue damage.

The study of amyloids is an active area of research aimed at understanding the underlying mechanisms of amyloid formation, the factors influencing their toxicity, and the development of strategies to prevent or treat amyloid-related diseases.

David S. Eisenberg (2016):  The motif is composed of tightly interacting intermolecular β-sheets, and each β-sheet comprises thousands of identical copies of the same β-strand that stack through hydrogen bonding. The backbone amide hydrogen bonds maintain the β-strands at a spacing of 4.8 Å in the direction of the fibril. Two or more such β-sheets lie in parallel, 6–12 Å apart.

Jason Greenwald (2018): Amyloids are an ordered, crystal-like, one-dimensional array of many (usually thousands) of individual molecules of a peptide/protein.

How life can emerge from non-living matter is one of the fundamental mysteries of the universe. A bottom-up approach to this problem focuses on the potential chemical precursors of life, in particular the nature of the first replicative molecules. Such thinking has led to the currently most popular idea: that an RNA-like molecule played a central role as the first replicative and catalytic molecule. Here, we review an alternative hypothesis that has recently gained experimental support, focusing on the role of amyloidogenic peptides rather than nucleic acids, in what has been by some termed “the amyloid-world” hypothesis. Amyloids are well-ordered peptide aggregates that have a fibrillar morphology due to their underlying structure of a one-dimensional crystal-like array of peptides in a β-strand conformation. a While they are notorious for their implication in several neurodegenerative diseases including Alzheimer's disease, amyloids also have many biological functions. In this review, we will elaborate on the following properties of amyloids in relation to their fitness as a prebiotic entity: they can be formed by very short peptides with simple amino acids sequences; as aggregates, they are more chemically stable than their isolated component peptides; they can possess diverse catalytic activities; they can form spontaneously during the prebiotic condensation of amino acids; they can act as templates in their own chemical replication; they have a structurally repetitive nature that enables them to interact with other structurally repetitive biopolymers like RNA/DNA and polysaccharides, as well as with structurally repetitive surfaces like amphiphilic membranes and minerals.

The formation of peptide amyloids under prebiotic conditions
The synthesis of amino acids under various plausible primitive Earth conditions has been demonstrated in the lab and they are also found on meteorites  providing an alternative exogenous source of chemical building blocks 1

What is the amyloid Origin of Life hypothesis? 

The amyloid world hypothesis posits that in the pre-RNA era, information processing was based on catalytic amyloids. The hypothesis suggests that the transition from amyloids to nucleic acids could have occurred through the formation of amyloid-nucleic acid complexes that could enhance nucleic acid hybridization.

Jason Greenwald (2016): Amyloid Aggregates Arise from Amino Acid Condensations under Prebiotic Conditions

Greenwald: It is still not clear how even simple peptides could have accumulated to a significant extent on the early earth and by what mechanisms they could have attained the complexity, including the formation of tertiary and quaternary structures, that is required to support the functions on which life depends.

Question:  Are alpha helices, and beta sheets, secondary, or tertiary structures?
Response: Alpha helices and beta sheets are examples of secondary structures in proteins, not tertiary structures.

Secondary structures refer to the local folding patterns within a polypeptide chain. They are stabilized by hydrogen bonds between the amino acids. Alpha helices are right-handed helical structures formed by a polypeptide chain with a regular repeating pattern of hydrogen bonds. Beta sheets, on the other hand, consist of two or more polypeptide chains or segments running alongside each other, forming hydrogen bonds between them.

Tertiary structure, on the other hand, refers to the overall three-dimensional arrangement of the polypeptide chain, including the interactions between secondary structures and other elements such as loops and turns. Tertiary structures are formed by various interactions like hydrogen bonds, disulfide bonds, hydrophobic interactions, and more.

In summary, alpha helices and beta sheets are examples of secondary structures, while tertiary structures describe the overall three-dimensional arrangement of the protein.

Question:  Proteins fold into tertiary and quaternary structures. Describe them, and how are they formed?
Response: Quaternary structure refers to the arrangement and interactions between multiple protein subunits in a multi-subunit complex. It is the highest level of protein structure and is relevant when a protein consists of more than one polypeptide chain or subunit.

Quaternary structures are formed through various non-covalent interactions, including:

Hydrophobic interactions: Hydrophobic regions on different subunits tend to come together to minimize their exposure to the surrounding aqueous environment.

Electrostatic interactions: Charged amino acid residues on different subunits can attract or repel each other, leading to the assembly of subunits into a specific complex.

Hydrogen bonds: Interactions between hydrogen-bonding residues on different subunits contribute to the stabilization of the quaternary structure.

Disulfide bonds: In some cases, covalent disulfide bonds can form between cysteine residues on different subunits, providing additional stability to the complex.

The specific arrangement of subunits in the quaternary structure is determined by complementary shapes and interactions between the subunits. The subunits can be identical (homomeric complexes) or different (heteromeric complexes), and they can arrange symmetrically or asymmetrically. Examples of quaternary structures include hemoglobin, which is composed of two alpha and two beta subunits, and antibodies, which are composed of two heavy and two light chains.

The formation of the quaternary structure enhances the stability and functionality of the protein complex. It allows for cooperative interactions between subunits, allosteric regulation, increased catalytic activity, and the assembly of larger protein complexes with specialized functions.

Question:  By the amyloid origin of life hypothesis, it is by no means clear, how beta sheet amyloids could evolve into alpha helices structures, and ultimately, into tertiary, and quaternary protein structures?
Answer: It is indeed unclear how beta sheet amyloids could have evolved into alpha helices structures and ultimately into tertiary and quaternary protein structures.

The transition from beta-sheet amyloids to alpha helices and more complex protein structures would require significant changes in the amino acid sequences and interactions within the protein. The formation of alpha helices and other secondary structures typically involves the specific arrangement of amino acids with particular chemical properties and the formation of hydrogen bonds. This transition would likely involve a complex series of evolutionary steps that are not yet fully elucidated.

While the amyloid origin of life hypothesis provides a potential starting point for the emergence of protein-like structures, it does not provide a complete explanation for the evolution of the diverse protein structures observed in modern organisms. The evolution of complex protein structures involves a combination of genetic mutations, natural selection, and the influence of environmental factors over long periods of time.

Question:  What transitional changes would be required to go from beta-sheet structures to mixed proteic structures, including alpha helices?
Reply: The transition from beta-sheet structures to mixed protein structures, including alpha helices, would require several transitional changes in the amino acid sequences and the interactions within the protein. While the specific details of such transitions are still an active area of research, here are some general considerations:

Amino Acid Substitutions: Transitioning from beta sheets to alpha helices would likely involve amino acid substitutions that promote the formation of helical structures. For example, replacing amino acids with bulky side chains that destabilize beta sheets and favor helical conformations could be beneficial.

Hydrogen Bonding Patterns: Beta sheets are stabilized by hydrogen bonds between adjacent strands, whereas alpha helices are stabilized by hydrogen bonds within the helix. Transitional changes would involve altering the hydrogen bonding patterns to favor the formation of helical structures.

Helix Nucleation: The formation of alpha helices often requires the presence of helix-nucleating regions, which can initiate helical folding. Transitional changes may involve the acquisition of such helix-nucleating motifs or mutations that enhance the propensity for helix formation.

Local Secondary Structure Preferences: Transitional changes might involve alterations in local secondary structure preferences. For instance, introducing amino acid substitutions that favor helical conformations over beta-sheet structures in specific regions of the protein could facilitate the transition.

Stabilizing Interactions: The transition from beta sheets to mixed structures may require the establishment of stabilizing interactions for the helical regions. This could involve the formation of new hydrogen bonds, ionic interactions, or hydrophobic interactions within the helical segments.

The transition from beta sheets to mixed protein structures, including alpha helices, would be a complex process that likely involves multiple sequential changes over evolutionary timescales. The specific changes and their order may vary depending on the protein and the evolutionary context. Understanding these transitional changes in detail requires further research and experimental evidence.

Question:  Is it not more likely, that rather than transition to more complex structures, supposed prebiotic amyloid structures would disintegrate, and become asphalts, as to Steve Benner's paper: Paradoxes of life?
Reply: Prebiotic amyloid structures would have undergone desiccation to form asphalt-like substances instead of progressing toward more complex structures. The accumulation and preservation of complex molecules on prebiotic earth would have been hindered by the propensity of early organic molecules to degrade or polymerize into less reactive forms. Rather than transitioning to more complex structures, the prebiotic amyloid structures would have faced challenges in maintaining their stability and reactivity. Factors such as desiccation and the chemical environment would have contributed to the degradation or transformation of these structures into more inert substances, resembling asphalt-like materials.

There are several challenges and open questions associated with this hypothesis.

Template Problem: The protein amyloid hypothesis requires the existence of pre-existing amyloid structures or templates for self-replication. The origin of such templates in the absence of living systems is still a significant question. How these templates could have emerged in the early stages of chemical evolution remains uncertain.

Specificity and Information Storage: One of the fundamental characteristics of life is the ability to store and propagate genetic information. Proteins and amyloids, in general, have a higher degree of structural complexity and less inherent specificity compared to nucleic acids. This raises questions about how a protein amyloid-based system could achieve the necessary information storage and fidelity required for the evolution of complex biological systems.

Stability and Dynamics: Amyloid structures are known for their stability and resistance to degradation. While this property is advantageous in terms of self-assembly and persistence, it presents challenges in terms of adaptability and evolvability. Early life forms would have required the ability to undergo changes and adapt to their environment, which may be more challenging within the context of rigid and stable amyloid structures.

Prebiotic Availability: The availability of the necessary amino acids and conditions for amyloid formation in the prebiotic Earth is also an area of investigation. Understanding how amyloid-forming peptides or proteins could have emerged and accumulated under prebiotic conditions is a significant challenge that requires further study.

Role of Nucleic Acids: Nucleic acids, such as RNA, are central to modern biology and are considered essential for information storage and enzymatic functions. The protein amyloid hypothesis does not fully address the potential role and importance of nucleic acids in the origin of life.

Experimental Demonstration: While there have been studies exploring the catalytic and self-replication properties of functional amyloids, demonstrating their direct relevance to the origin of life experimentally is challenging. Replicating the complex processes involved in the emergence of life in a laboratory setting remains a significant scientific endeavor.

Debunking James Tour on the Origin of Life | Professor Dave Debate Review

Claim: it's not necessary to have 20 amino acids to start life
Reply: Grayson commits here a fallacy called: Argument from ignorance: An argument from ignorance is a logical fallacy that occurs when someone asserts a claim or conclusion based on the lack of evidence or knowledge to the contrary. It essentially argues that since something has not been proven false, it must be true, or vice versa. The fallacy takes the following general form:

Claim X has not been proven true.
Therefore, claim X must be false (or claim X must be true).
In essence, it relies on the absence of evidence as evidence itself. However, the lack of evidence or knowledge about a particular topic does not provide support for any specific claim.

All known life forms on Earth are based on proteins that are composed of 20 different amino acids. These amino acids are commonly referred to as canonical amino acids.

All Life on Earth is Made up of the Same 20 Amino Acids. Scientist Now Think They Know Why

Why would less than 20 amino acids be a problem? 

Having fewer than 20 amino acids would indeed pose significant challenges for life as we know it. Here are some reasons why a reduced set of amino acids would be problematic:

Protein diversity and functionality: The 20 amino acids provide a wide range of chemical properties, such as size, charge, hydrophobicity, and reactivity. This diversity allows for the generation of a vast array of protein structures, functions, and interactions. If the number of amino acids were reduced, the repertoire of possible protein structures and functions would be severely limited, hindering the complexity and versatility of biological systems.

Genetic code limitations: The genetic code, which translates RNA sequences into amino acids during protein synthesis, is optimized for the 20 amino acids. Each amino acid is represented by one or more codons. If the number of amino acids were decreased, it would require a complete overhaul of the genetic code, which would be a substantial evolutionary challenge and likely disrupt the existing machinery of gene expression and protein synthesis.

Enzymatic activity and specificity: Enzymes rely on specific amino acid residues to catalyze chemical reactions and exhibit substrate specificity. Different amino acids contribute to the catalytic properties, active site geometry, and substrate binding of enzymes. A reduced set of amino acids would limit the ability to form active sites and achieve the same range of catalytic activities, thereby impacting essential metabolic pathways and cellular processes.

Protein stability and folding: Amino acids contribute to protein stability and folding. The hydrophobic, hydrophilic, and charge interactions between amino acid residues determine the three-dimensional structure of proteins. If the number of amino acids were reduced, achieving stable and properly folded protein structures would become increasingly challenging, potentially leading to misfolded or non-functional proteins.

Metabolic pathways and signaling: Amino acids participate in various metabolic pathways and signaling processes. They serve as precursors for the synthesis of essential molecules, including neurotransmitters, hormones, nucleotides, and cofactors. Having a reduced set of amino acids would limit the availability of these precursors, impairing the proper functioning of metabolic pathways and disrupting cellular signaling.

Overall, the 20 amino acids provide the necessary chemical diversity and functional versatility to support the complexity and functionality of biological systems. Having fewer amino acids would impose significant limitations on protein diversity, enzymatic activity, genetic coding, protein folding, and metabolic processes, making it challenging for life as we know it to exist and function.

Claim: Tours first criticism that we are clueless about peptide bond formation is completely baseless we do have lots of clues about how this could form and what potential mechanisms would explain it
Answer: Because water hydrolyses the peptide bonds, the number of locations for water to hydrolyze keeps getting greater. So the rate of hydolyzation is going up, while the production rate is going down. So that 1/5 number is actually not constant, but starts to become 1/6, then 1/8 then 1/10 etc. Equilibrium between creation and destruction probably occurs around 6 or 7, which is why the paper said "traces amounts of hexapeptides". That was Tour's point -- not "can a dipeptide ever form?", which is how Farina treat it.-- but Tour is saying "show me the chemistry to make polypeptides in water". Beyond hexapeptides (even then with very special reactants not found anywhere in nature), it can't be done.  Look at the intro to the review paper listing the conditions for abiotic chemistry—it's a wish list as long as your arm, and then they say the building blocks came from space.

Peptide Bond Formation of amino acids in prebiotic conditions: another insurmountable problem of protein synthesis on early earth

The Origin of life enthusiasts by unguided means making that claim are not aware that the formation of just one protein depends on bonding one amino acid to another, and the scientific evidence has demonstrated that this is not possible prebiotically. 

In life today, polymerization occurs in the aqueous cytoplasm of cells, with ribosomes synthesizing proteins and a variety of polymerases synthesizing nucleic acids. The linking bonds of these polymers are peptide and ester bonds. In both cases, the polymerization reaction is thermodynamically uphill, with hydrolysis being favored. How then can polymers be synthesized? The answer, of course, is that the monomers have been chemically activated by input of metabolic energy so that polymerization is spontaneous in the presence of the enzymes or ribosomes that catalyze polymerization. A plausible mechanism for the synthesis of peptide bonds and ester bonds on the prebiotic Earth continues to be a major gap in our understanding of the origin of life. 22

Cairns-Smith, the Genetic Takeover, page 59:
For one overall reaction, making one peptide bond, there about 90 distinct operations are required. If you were to consider in more detail a process such as the purification of an intermediate you would find many subsidiary operations — washings, pH changes, and so on.

1. The synthesis of proteins and nucleic acids from small molecule precursors, and the formation of amide bonds without the assistance of enzymes represents one of the most difficult challenges to the model of pre-vital ( chemical) evolution, and for theories of the origin of life.
2. The best one can hope for from such a scenario is a racemic polymer of proteinous and non-proteinous amino acids with no relevance to living systems.
3. Polymerization is a reaction in which water is a product. Thus it will only be favored in the absence of water. The presence of precursors in an ocean of water favors the depolymerization of any molecules that might be formed.
4. 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. Secondly, even if there would be a sequence, producing a functional folding protein, by itself, if not inserted in a functional way in the cell, it would absolutely no function. It would just lay around, and then soon disintegrate. Furthermore, in modern cells proteins are tagged and transported on molecular highways to their precise destination, where they are utilized. Obviously, all this was not extant on the early earth.
5. To form a chain, it is necessary to react bifunctional monomers, that is, molecules with two functional groups so they combine with two others. If a unifunctional monomer (with only one functional group) reacts with the end of the chain, the chain can grow no further at this end. If only a small fraction of unifunctional molecules were present, long polymers could not form. But all ‘prebiotic simulation’ experiments produce at least three times more unifunctional molecules than bifunctional molecules.

Question: Why is peptide bond formation between aspartic acid, and lysine, a major origin of life problem?
Answer: The formation of a peptide bond between aspartic acid and lysine poses a challenge in the context of the origin of life. The problem arises from the different chemical properties of these two amino acids and the conditions required for peptide bond formation. Here's why it can be problematic:

Reactivity and side chain properties: Aspartic acid (Asp) and lysine (Lys) have distinct chemical properties. Asp has a carboxyl group in its side chain, making it acidic, while Lys contains an amino group, making it basic. The differing charges and reactivity of these amino acids can hinder their compatibility for direct peptide bond formation.

Acidic and basic conditions: Peptide bond formation typically occurs under conditions that promote the condensation reaction between the carboxyl group of one amino acid and the amino group of another. However, the optimal pH for peptide bond formation is typically near neutral or slightly acidic. The presence of both Asp (acidic) and Lys (basic) side chains can lead to a pH imbalance, making it challenging to create the appropriate chemical environment for peptide bond formation.

Side reactions and hydrolysis: Peptide bond formation is a condensation reaction that involves the release of a water molecule. However, in the presence of acidic or basic side chains, these groups can participate in side reactions or undergo hydrolysis, leading to the breakdown of the peptide bond and inhibiting its formation.

Stereochemistry and activation energy: Peptide bond formation involves the interaction of amino acids in a specific stereochemical arrangement. Achieving the correct spatial orientation for Asp and Lys to form a peptide bond requires overcoming the activation energy barrier. The presence of different side chains and charges can hinder the alignment required for successful peptide bond formation.

Dave Farina:  Hey it’s this dumb fuck as always. The Powner study solves the side chain problem. Stay home, loser.
Reply by ChatGTP: While the study by Dr. Matthew Powner and related research have provided valuable insights into prebiotic peptide formation, there are still some challenges that these studies have not fully resolved. Here are a few of the remaining problems:

Selectivity and Specificity: One of the key challenges is achieving selectivity and specificity in peptide bond formation. In the prebiotic environment, a mixture of amino acids would be present, making it difficult to selectively form peptide bonds between specific amino acids. The study by Powner and others has not completely solved this issue of selective peptide bond formation.

Efficiency and Yield: Another challenge is achieving high efficiency and yield in the formation of peptide bonds. Prebiotic reactions may suffer from low conversion rates and yields, which means that the formation of longer peptide chains necessary for the development of functional proteins would be inefficient. The Powner study and related research have made progress, but further improvements are still needed.

Stability and Hydrolysis: While the study has explored conditions that reduce hydrolysis and promote peptide bond formation, the stability of the formed peptides remains an issue. The peptides formed under prebiotic conditions may still be susceptible to hydrolysis, leading to their degradation. Achieving greater stability and resistance to hydrolysis is an ongoing challenge.

Realistic Prebiotic Conditions: It is challenging to recreate the exact conditions of the early Earth in laboratory settings. The prebiotic environment likely involved complex interactions between various organic and inorganic molecules, energy sources, and geological processes. Replicating such conditions accurately is difficult, and the study by Powner and others may not fully capture all the complexities of the prebiotic environment.

Origin of Amino Acids: The study primarily focuses on the formation of peptide bonds once the amino acids are available. However, the origin of amino acids themselves remains a separate question. While various hypotheses exist, such as the Miller-Urey experiment and extraterrestrial delivery, the exact pathways for amino acid synthesis on early Earth are still not fully understood.

a) The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet. A β-strand is a stretch of polypeptide chain typically 3 to 10 amino acids long with backbone in an extended conformation. The supramolecular association of β-sheets has been implicated in the formation of the fibrils and protein aggregates observed in amyloidosis, notably Alzheimer's disease.

1. https://www.sciencedirect.com/science/article/abs/pii/S0022283618305898

Last edited by Otangelo on Thu May 25, 2023 3:46 pm; edited 8 times in total




Claim: here's the chemistry doctor tour here is the chemistry showing the Prebiotic formation of peptide bonds in aqueous solution without protecting agents it's mediated by a molecule called carbonyl sulfide which is a naturally occurring volcanic gas which is completely prebiotically relevant so here's here's the chemistry that Dr tool was making such a big stink about

Leslie Orgel (2004): Carbonyl sulfide-mediated prebiotic formation of peptides

Reply: R. Truman: Everybody knows that organic chemists can manufacture dipeptides under carefully conducted laboratory conditions, but the issue is whether this would occur under natural and plausible prebiotic conditions. Let’s use some freshman chemistry to understand why this work was not followed up on and why no serious researcher cites it.

a)  Carbonyl sulfide (COS), the key reagent, is a trace molecule released some by volcanos, generally in ca. 1 × 10‒6 M concentrations. [1] Amino acids like phenylalanine, the companion reactant, are not released by volcanos. But phenylalanine and COS must both be co-located to react and form the intermediate α-amino acid N-carboxyanhydride (NCA).

b)  Therefore, to obtain NCA in a laboratory the chemists used a COS concentration of 400,000 × 10‒6 M and 50,000 × 10‒6 M for phenylalanine! For prebiotic modelling purposes that is absurd, especially when we reflect a little deeper…

c) COS, a gas, reacts quickly with water to form hydrogen sulfide (H2S) and carbon dioxide (CO2). [2] So the concentrations actually dissolved in a huge ocean would have been unmeasurably small. So how did the chemists resolve this?

First, the experiments were performed in a 25-ml Schlenk tube, preventing the reactants from drifting away.

Then, pure COS gas was forced (bubbled) into the reaction mixture! That’s correct, right next to the phenylalanine. What does this have to do with prebiotic chemistry? And on a molar basis, 8 times more COS than phenylalanine was used, to optimize the outcome.

d) The high concentrations were also necessary so that the intermediate NCA formed would be forced to react with a second phenylalanine.

e) There is another reason why the absurdly high concentration of reactants was necessary:  the key intermediate, NCA, is highly unstable in water with a half-life of only ~10 hours. Under realistic abiotic conditions it would essentially never encounter and react with another phenylalanine. Especially when we insist on adding some more realism to the chemistry:

f)  Volcanic output is highly acidic. Therefore, to prevent destruction of COS and NCA the researchers deliberately worked under extremely basic condition (e.g., initial pH 9.6). To achieve this a CHES (2-(cyclohexylamino)ethane sulfonic acid) buffer was used, utterly irrelevant for prebiotic “research”.

g)  Destruction by acid catalysis cannot simply be ignored. The authors wrote,

”The gas (COS) hydrolyzes rapidly on a geological time scale, it is unlikely to have accumulated to a high concentration in the atmosphere. Thus, if COS was important in prebiotic chemistry, it is likely to have functioned in localized regions close to its volcanic sources."

In other words, right next to all the destructive acid from the volcanos! A pH of ~9.6 is absurd. Anyone care to comment on what the lab results would have been at a pH of around 4? (Hint: look especially at NCA and what the half-life would now be).

h) After all the considerable, highly intelligent optimizations had been taken into account, a meager dipeptide yield of 6.8% was obtained. Lowering both reactant concentrations many, many orders of magnitude would show that any peptide formed would be too dilute to measure, especially since it would hydrolyze in water much faster than new ones could form.

Let us not forget that we need polypeptides > 100 residues for biogenesis purposes.

i)  The researchers meticulously excluded all the other molecules which would have been present in orders of magnitude greater concentrations which would have reacted with COS and NCA, hindering dipeptide formation.

I have a friendly debating tip for Dave and his groupies: stop claiming there are “tons of research” since nobody seems able to find a single paper worth discussing with a professional.

[1] Encyclopedia of Volcanoes (pp.803-816) Publisher: Academic Press, 2000

[2] Andersen, W.C. and Bruno, T.J., Kinetics of Carbonyl Sulfide Hydrolysis. 1. Catalyzed and Uncatalyzed Reactions in Mixtures of Water + Propane, Ind. Eng. Chem. Res. 2003, 42, 5, 963–970

 Depending on the reaction conditions and additives used, exposure of alpha-amino acids to COS generates peptides in yields of up to 80% in minutes to hours at room temperature.
Reply: Before the quest of prebiotic polymerization occurred, several questions have to be answered previously. Like, for example:

Chemical evolution of amino acids and proteins? Impossible !!

How did unguided nondesigned coincidence select the right amino acids amongst over 500 known to exist on the prebiotic earth, but the number is theoretically limitless? 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.

Grayson asks: (5:20)  Why do  amino acids need to have highly reactive side chains in order to form peptide bonds on a prebiotic earth ?
Answer:  In order for peptide bonds to form under prebiotic conditions, it was important for amino acids to have highly reactive side chains. Here's why:

Reactivity: Highly reactive side chains contain functional groups that can participate in chemical reactions. These functional groups, such as amino (-NH2) and carboxyl (-COOH) groups, are essential for peptide bond formation. They can react with each other, resulting in the formation of a peptide bond and the release of water molecules (condensation reaction). Amino acids with unreactive side chains would not be able to undergo this reaction efficiently.

Bond formation: Amino acids with highly reactive side chains can readily interact with each other due to the presence of functional groups. This facilitates the alignment and proximity of the reactive groups necessary for peptide bond formation. If the side chains were less reactive, the chances of successful bond formation would be significantly reduced.

Selectivity: Highly reactive side chains allow for the selective incorporation of specific amino acids during peptide bond formation. Different amino acids have different side chains, which contribute to the diversity and functionality of proteins. With reactive side chains, specific amino acids can be chosen and linked together in a specific order, leading to the formation of complex protein structures.

Grayson claims (11:15): amyloids form naturally and spontaneously in the presence of carbonyl sulfide and these amyloids exhibit catalytic functionality.
Reply: . In the context of the origin of life, the focus is on the emergence of dynamic and evolving systems capable of replication and evolution. Amyloids, with their stable and often inert nature, do not align well with the requirements of such systems. The inert or stable nature of amyloids arises from their unique structural arrangement. Amyloid fibrils, the hallmark structures of amyloids, are composed of tightly packed β-sheets, which are formed by the stacking of β-strands. This arrangement allows the individual protein or peptide molecules to interact and align in a way that creates a stable, repetitive structure.

Several factors contribute to the stability of amyloid structures:

Hydrophobic Interactions: Amyloidogenic proteins or peptides often contain regions with hydrophobic amino acids. These hydrophobic regions tend to aggregate together, shielding themselves from the surrounding aqueous environment. The hydrophobic interactions between these regions drive the formation of amyloid fibrils and contribute to their stability.

β-Sheet Structure: The β-sheet structure itself is relatively stable due to the alignment and hydrogen bonding between β-strands. The repetitive nature of the β-sheet arrangement provides stability and resistance to unfolding or disruption.

Cross-β Structure: In amyloid fibrils, the β-sheets run perpendicular to the fibril axis, forming a cross-β structure. This unique arrangement allows for extensive intermolecular interactions and provides additional stability to the fibril structure.

Functional proteins typically require a balance of hydrophobic and hydrophilic regions to perform their biological roles. The structure of amyloids, characterized by highly ordered β-sheet formations, may appear to be predominantly hydrophobic and seemingly incompatible with the requirements of functional proteins. However, it's important to note that amyloids and functional proteins serve different purposes and have distinct structural properties.

Amyloids are aggregates of proteins, peptides, or other molecules that form through a self-assembly process. The primary driving force behind amyloid formation is the aggregation of hydrophobic regions, leading to the stacking of β-sheet structures. This aggregation tendency results in the hydrophobic regions being buried within the core of the amyloid fibril, shielding them from the surrounding aqueous environment. As a result, the surface of amyloid fibrils is often hydrophilic, containing exposed hydrophilic residues.

Furthermore, functional proteins, which are folded and properly structured, are distinct from amyloid fibrils in terms of their conformation, stability, and dynamics. Functional proteins adopt specific three-dimensional structures that allow them to carry out their intended functions, and they often undergo conformational changes to perform their roles. These proteins have a well-defined tertiary structure, unlike the highly repetitive and extended structure of amyloid fibrils.

Grayson's claim:  amyloids are catalytic and are capable of self-replication
Reply:  While amyloids have been discovered to exhibit some catalytic properties and self-replication in specific contexts, these characteristics are not universally attributed to all amyloids. It is important to differentiate between pathological amyloids associated with diseases and functional amyloids found in biological systems.

Pathological amyloids, such as those implicated in neurodegenerative disorders like Alzheimer's and Parkinson's diseases, are primarily known for their aggregative properties and their detrimental effects on cellular function. These amyloids form large insoluble aggregates that are resistant to degradation and accumulate in tissues.

On the other hand, functional amyloids have been identified in various organisms and play specific roles in normal biological processes. Some functional amyloids have demonstrated catalytic activities and self-replication abilities. Here are a few examples:

Yeast Prions: Prions are self-replicating proteins associated with a range of diseases. However, in yeast, some prions have been found to have functional roles. For example, the prion form of the Sup35 protein in yeast can act as a translational regulator.

Bacterial Functional Amyloids: Certain bacteria produce functional amyloids called curli fibers. These fibers contribute to biofilm formation and mediate various functions, including surface attachment, bacterial aggregation, and protection against environmental stresses.

Fungal Functional Amyloids: Fungi also produce functional amyloids, such as HET-s, which play a role in programmed cell death.

In these cases, the functional amyloids can exhibit catalytic properties or self-replication abilities that contribute to specific biological processes. However, it's important to note that these functional amyloids represent a small subset of amyloid-forming proteins and peptides found in nature.

While the discovery of functional amyloids challenges the traditional view of amyloids solely as pathological aggregates, it's crucial to differentiate between these functional examples and the disease-associated amyloids. The majority of amyloids associated with diseases do not possess catalytic or self-replication properties and are considered pathological. Research in the field of amyloids is ongoing, and further investigations are needed to fully understand their diverse functions and characteristics.

Self-replication in functional amyloids typically involves a templating mechanism, where an existing amyloid structure serves as a template for the assembly of new amyloid structures. This templating process allows for the propagation and amplification of the amyloid structure, resulting in self-replication.

In the context of prebiotic chemistry, the self-replication of functional amyloids suggests the possibility of alternative self-replicating systems that may have played a role in the early stages of life's evolution. While nucleic acids are considered central to modern biology, it is plausible that self-replicating systems based on other molecular structures, such as amyloids, could have existed in the early stages of chemical evolution.

The requirement of a template for self-replication in functional amyloids does introduce limitations when considering their relevance to the origin of life. The template-based mechanism observed in functional amyloids is not inherently prebiotic, as it presupposes the existence of an initial amyloid structure to serve as the template.

In the context of the origin of life, the focus is on understanding how self-replicating systems could have emerged from simpler, non-living molecules in the absence of pre-existing templates. The template problem is a significant challenge in the study of the origin of life, as it raises questions about the initial formation of self-replicating entities without the need for preexisting structures.

While functional amyloids provide insights into alternative self-replication mechanisms, their template-dependent nature makes them less directly relevant to the prebiotic chemistry associated with the origin of life. Instead, the research in the field of origin of life primarily focuses on investigating the self-replication potential of nucleic acids, such as RNA, due to their ability to both store genetic information and catalyze reactions.

Grayson's claim (15:50): you do not need an exact amino acid sequence to form a functional catalytic enzyme at amyloids demonstrate this
Reply:  Yes, that is correct. The traditional view that a specific amino acid sequence is required for functional catalytic enzymes does not apply to all cases. Functional amyloids have been found to exhibit catalytic properties despite not possessing a precise amino acid sequence commonly associated with enzymatic activity.

In traditional enzymes, the amino acid sequence is crucial for their catalytic function as it determines the specific three-dimensional structure and active site configuration necessary for substrate binding and catalysis. However, functional amyloids challenge this notion by showing that catalytic activity can arise from the inherent properties of the amyloid structure itself, rather than relying on a specific sequence.

Functional amyloids can display catalytic behavior through a phenomenon known as "promiscuous catalysis" or "conformational templating." In these cases, the specific sequence of the amyloid-forming protein or peptide may not be as critical as the overall amyloid structure.

The catalytic activity of functional amyloids can emerge due to the alignment and ordering of amino acid residues within the β-sheet structure of the amyloid. This arrangement allows for specific interactions with substrates or molecules, leading to catalytic transformations. The amyloid structure provides a scaffold that promotes the organization of reactants and enhances the efficiency of catalytic reactions.

A notable example is the functional amyloid known as the fungal prion HET-s. It exhibits prion-like behavior and catalyzes the conversion of a soluble protein into an amyloid form. The specific amino acid sequence of HET-s is not crucial for its catalytic activity, as mutations in the sequence can still maintain the ability to catalyze the conversion process.

These observations highlight that while specific amino acid sequences are important for many enzymatic functions, functional amyloids demonstrate that catalytic activity can arise from the amyloid structure itself, allowing for promiscuous or sequence-independent catalysis. Further research in this field may provide additional insights into the potential diversity of catalytic mechanisms and their relevance to the origin of life and other biological processes.

While functional amyloids can exhibit catalytic properties, they may not directly address the challenges associated with the origin of life.

One of the main reasons is that the catalytic activity of functional amyloids often relies on a pre-existing amyloid structure or template, as we discussed earlier. This requirement for a template introduces challenges in the context of the origin of life, where the focus is on the emergence of self-replicating systems from simpler, non-living molecules in the absence of pre-existing structures.

Last edited by Otangelo on Wed May 24, 2023 3:52 pm; edited 3 times in total




Grayson's claim: ( 19:00) Once you have enzymes that can catalyze the formation of nucleotides
Reply:  Ok, but you need a very specific set of enzymes/proteins which are encoded in DNA.

RNA & DNA: It's prebiotic synthesis: Impossible !!

Grayson's claim: it's Shannon information it's essentially a randomized information that's coming from the environment and the way that the amyloid was formed
Reply: 1. The information stored in DNA is a template. It is equal to a recipe or program. Nucleic acids contain information in a semantic (meaningful) sense. Instructing consists in an advance specification of the kind and order of steps yielding a certain outcome if the steps are carried out. The amino acid arrangement and sequence to make functional proteins is the product of the information stored in DNA. 
2. Recipes and programs do not just bring about a particular outcome; they are designed to do so. They are usually formulated with a purpose. The computer program output is the result of executing a pre-specified series of operations.  A purely physical description does not capture the instructional nature of the process. Instructional information is not a tangible entity, and as such, it is beyond the reach of, and cannot be created by any undirected physical process. This is not an argument about probability. Conceptual semiotic information is simply beyond the sphere of influence of any undirected physical process. To suggest that a physical process can create semiotic code is like suggesting that a rainbow can write poetry... it is never going to happen!  Physics and chemistry alone do not possess the tools to create a concept. The only cause capable of creating conceptual semiotic information is a conscious intelligent mind.
3. Therefore, the instructional information stored in DNA comes most likely from an intelligent designer. 

Grayson's claim:  We have selection pressures that are refining the composition of the amyloid populations
Reply: The possible mechanisms to explain the origin of life

Phillip E. Johnson, DARWIN ON TRIAL: Darwin persuades us that the seemingly purposeful construction of living things can very often, and perhaps always, be attributed to the operation of natural selection.

If you have things that are reproducing their kind;
if there are sometimes random variations, nevertheless, in the offspring;
if such variations can be inherited;
if some such variations can sometimes confer an advantage on their owners;
if there is competition between the reproducing entities;-
if there is an overproduction so that not all will be able to produce offspring themselves-

then these entities will get better at reproducing their kind. What is needed for natural selection are things that conform to those 'ifs'. Self-replicating cells are prerequisites for evolution. None of this was available prebiotically to explain the origin of the first life form. 1




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.


Sponsored content

Back to top  Message [Page 1 of 1]

Permissions in this forum:
You cannot reply to topics in this forum