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


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Abiogenesis is mathematically impossible

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2.4  Stability and Reactivity: The Prebiotic Amino Acid Paradox

The origin of life theories faces a significant challenge in explaining how amino acids could have remained stable enough to accumulate in prebiotic environments while simultaneously being reactive enough to form peptides without enzymatic assistance. This analysis examines the stability-reactivity paradox and its implications for naturalistic explanations of abiogenesis. The stability-reactivity paradox concerning the prebiotic amino acid environment is a crucial aspect in understanding abiogenesis. Research has shown that amino acids exhibit varying stability in aqueous solutions at different temperatures, with half-lives ranging from a few days to several years, depending on the specific amino acid and environmental factors [12]. Additionally, the formation of peptides without enzymatic assistance is a significant challenge, as dehydration to form amide bonds is highly unfavorable in water [13]. However, recent studies have demonstrated unique reactivity of free amino acids at the air-water interface, leading to the rapid formation of peptide isomers on a millisecond scale under ambient conditions, showcasing the potential for abiotic peptide synthesis in aqueous environments [13]. These findings shed light on the delicate balance between stability and reactivity that must have existed in the prebiotic world to enable the accumulation of amino acids and the formation of essential biomolecules.

Quantitative Challenges
Studies on amino acid stability in aqueous solutions at various temperatures reveal a half-life ranging from a few days to several years, depending on the specific amino acid and environmental conditions (Radzicka & Wolfenden, 1996). For instance, at 25°C and neutral pH, the half-life of aspartic acid is approximately 253 days, while that of tryptophan is about 74 days. However, these half-lives decrease dramatically at higher temperatures, which are often invoked in prebiotic scenarios. At 100°C, most amino acids have half-lives of less than a day.

Conversely, the rate of spontaneous peptide bond formation between amino acids in aqueous solutions is extremely slow. Experimental studies have shown that the half-time for dipeptide formation at 25°C and pH 7 is on the order of 10^2 to 10^3 years (Martin et al., 2007). This presents a significant kinetic barrier to the formation of even short peptides under prebiotic conditions.

Implications for Current Models
These quantitative findings challenge the plausibility of current models for prebiotic peptide formation. The disparity between the rates of amino acid decomposition and peptide bond formation suggests that in most prebiotic scenarios, amino acids would degrade faster than they could polymerize into functionally relevant peptides. This stability-reactivity paradox undermines the assumption that simple accumulation of amino acids in a primordial soup could lead to the spontaneous emergence of proto-proteins.

Requirements for Natural Occurrence
For the stability and reactivity of prebiotic amino acids to support the emergence of life, the following conditions must be simultaneously met:

1. Protection mechanisms against hydrolysis and thermal decomposition
2. Sufficient reactivity to form peptide bonds without enzymatic catalysis
3. Selective polymerization to form functional peptide sequences
4. Prevention of side reactions leading to unusable byproducts
5. Maintenance of a pH range that balances stability and reactivity (typically pH 7-9)
6. Temperature conditions that allow for both stability and reactivity
7. Presence of activating agents to facilitate peptide bond formation
8. Absence of competing molecules that could interfere with polymerization
9. Mechanisms to remove water, driving peptide bond formation
10. Recycling processes to regenerate degraded amino acids

These requirements must coexist in a prebiotic environment, presenting a formidable challenge to naturalistic explanations. Several of these conditions are mutually exclusive or contradictory. For example, the need for protection against hydrolysis (point 1) conflicts with the requirement for sufficient reactivity (point 2). Similarly, the presence of activating agents (point 7) often leads to increased rates of side reactions (conflicting with point 4).

The stability-reactivity paradox is further illustrated by the "aspartic acid problem." Aspartic acid, a crucial amino acid in many proteins, is particularly prone to cyclization reactions, forming unreactive succinimide derivatives. Studies have shown that at pH 7 and 37°C, about 4% of aspartic acid residues in a peptide chain will convert to succinimides within 24 hours (Geiger & Clarke, 1987). This cyclization not only removes aspartic acid from the pool of available monomers but also disrupts the integrity of any formed peptides.

The requirement for water removal to drive peptide bond formation (point 9) contradicts the aqueous environment typically assumed in prebiotic scenarios. Proposed solutions, such as wet-dry cycles or mineral surface catalysis, introduce additional complexities and limitations.

The stability and reactivity requirements for prebiotic amino acids present substantial challenges to current naturalistic explanations for the origin of life. Future discussions on this topic should focus on:

1. Developing more realistic models that account for the stability-reactivity paradox.
2. Investigating novel mechanisms that could simultaneously protect and activate amino acids.
3. Exploring the potential role of non-aqueous environments in early peptide formation.
4. Addressing the mutual exclusivity of certain required conditions in prebiotic scenarios.
5. Critically examining the assumptions underlying current abiogenesis hypotheses in light of these kinetic and thermodynamic challenges.

By rigorously addressing these points, the scientific community can work towards a more comprehensive and evidence-based understanding of the chemical processes that could have led to the emergence of life.

2.5 Thermodynamic and Kinetic Barriers to Polymerization

The challenges of polymerization in water, especially for polypeptides like [Gly]n, are well-documented due to both thermodynamic and kinetic barriers, leading to equilibrium concentrations as low as < 10^-50 M at temperatures of 25° - 37°, making the existence of even short polypeptides like [Gly]9 highly improbable [14] [15]. Recent studies by Dr. Royal Truman, Dr. Charles McCombs, and Dr. Change Tan further emphasize the difficulties by outlining nine additional requirements for OoL-relevant polypeptides, including the need for specific sequences, three-dimensional structures, continuous production, and self-replication, all of which pose significant challenges under natural conditions [14]. These stringent requirements, such as the need for about 300 amino acids to form proteins and the exclusion of nonbiological amino acids, highlight the complex interplay of factors that must be simultaneously satisfied for peptides/proteins to be relevant in origin-of-life scenarios, presenting a formidable obstacle for OoL discussions [14].

Polypeptides do not form in water at any temperature for thermodynamic and kinetic reasons
Detailed quantitative analysis shows extremely low equilibrium concentrations of even short polypeptides
The concentration of [Gly]9 would converge to < 10^-50 M at equilibrium in water at temperatures of 25° - 37°
Nine additional requirements for OoL-relevant polypeptides are outlined, all of which violate fundamental chemical and statistical principles under unguided, natural conditions

In two recent ground-breaking reports, senior scientists Dr. Royal Truman, Dr. Charles McCombs, and Dr. Change Tan examined the polymerization of amino acids in water, using kinetic and thermodynamic empirical data along with computer simulations. A detailed quantitative understanding was provided for the first time of how the concentrations of polypeptides decrease with length, using mostly the best-studied amino acid, glycine (Gly):
 
[Gly]n << [Gly]n-1 << [Gly]n-2 << [Gly]n-3 << [Gly]n-4 
 
The quantitative analysis showed that the concentration of [Gly]9 would converge to < 10^‒50 M at equilibrium in water at temperatures of 25° - 37°. In other words, not even one Gly9 would have existed on prebiotic earth, far less the necessary huge concentrations of much larger polypeptides required by origin of life (OoL) theories.
This is a devastating conclusion for the OoL community! To make matters even worse, if that were possible, the authors provided a table with nine more requirements polypeptides must all fulfill to be relevant for OoL purposes, all of which violate fundamental chemical and statistical principles under unguided, natural conditions.
To permit structured and productive OoL discussions the authors recommend beginning with this table, which applies also to RNA and DNA polymers, to decide which dilemma to discuss.

1. Many amino acids must be linked together, about 300 on average for proteins.
2. Only enantiomers of L-amino acids should be included.
3. Only linear polymers should form; that is, the side chains of the amino acids must not react.
4. Precise sequences of amino acid residues must be formed to perform useful functions.
5. Long chains must adopt a suitable three-dimensional structure.
6. Large numbers of peptide copies must be produced continuously for millions of years.
7. The correct proportion of peptides with a specific sequence must be colocalized.
8. Other molecules, including nonbiological amino acids, should be avoided in peptides.
9. The entire system or organism must self-replicate, including all necessary peptide copies. 10. The polymers and the three-dimensional structure must be formed under relevant conditions.
These 10 requirements must be met simultaneously for peptides/proteins to be relevant in origin-of-life scenarios, but there are contradictory trade-offs between many of these requirements. For example, raising the temperature to facilitate a Gly adding to Glyn to form Glyn+1 (requirement #1) would have the effect of accelerating the rate of racemization L-Gly  D-Gly (requirement #2).

3. Challenges in Prebiotic Protein Formation

3.1 Thermodynamic and Kinetic Barriers to Prebiotic Polypeptide Formation

The spontaneous formation of polypeptides in aqueous prebiotic environments encounters significant thermodynamic and kinetic barriers, challenging current naturalistic explanations for the origin of life. Thermodynamic calculations indicate that peptide bond formation in water is energetically unfavorable, with a standard Gibbs free energy change of approximately 3.5 kcal/mol at 25°C and pH 7 [16]. Computational exploration of organic molecule formation from water and hydrogen cyanide reveals diverse reactivity landscapes and lower activation energies for biologically relevant molecules, impacting the interpretation of network kinetics [17]. In fluctuating silica environments, the presence of water activity enhances peptide formation through hydration steps, resulting in the formation of self-assembled peptide aggregates with defined secondary structures [18]. Additionally, a new abiotic route demonstrates peptide chain growth from protonated glycine dimers in a cold gaseous atmosphere without the need for a solid catalytic substrate [19]. Experimental simulations under hydrothermal and extraterrestrial ice crystal environments show the formation of small functional peptides, shedding light on potential prebiotic pathways for catalytically active peptides [20].

Quantitative Challenges
Thermodynamic calculations reveal that the formation of peptide bonds in aqueous solutions is energetically unfavorable. The standard Gibbs free energy change (ΔG°) for peptide bond formation is approximately +3.5 kcal/mol at 25°C and pH 7 (Jakubke & Jeschkeit, 1977). This positive value indicates that the reaction is non-spontaneous under standard conditions.

Kinetic studies further compound this challenge. The rate constant for uncatalyzed peptide bond formation in water at 25°C is estimated to be around 10^-4 M^-1 year^-1 (Sievers & von Kiedrowski, 1994). In contrast, the rate constant for peptide bond hydrolysis under the same conditions is approximately 10^-9 to 10^-11 s^-1 (Radzicka & Wolfenden, 1996). These values translate to a half-life of peptide bond formation on the order of thousands of years, while the half-life for hydrolysis is typically days to months.

Implications for Current Models
These quantitative findings present severe challenges to current models of prebiotic polypeptide formation. The unfavorable thermodynamics imply that even if peptides were to form, they would be thermodynamically driven to hydrolyze back into amino acids. The slow kinetics of formation coupled with the relatively rapid hydrolysis suggests that maintaining any significant concentration of polypeptides in a prebiotic aqueous environment is highly improbable.

Requirements for Natural Occurrence
For the spontaneous formation and persistence of polypeptides in a prebiotic setting, the following conditions must be simultaneously met:

1. Energy input to overcome the unfavorable thermodynamics of peptide bond formation
2. Mechanisms to dramatically accelerate the rate of peptide bond formation
3. Protection against hydrolysis to maintain formed peptides
4. Concentration mechanisms to achieve sufficiently high local amino acid densities
5. Selective polymerization to form functional peptide sequences
6. Removal of water to drive the condensation reaction forward
7. pH conditions that balance peptide bond formation and stability (typically pH 2-5 for formation, pH 5-8 for stability)
8. Temperature regime that allows for both formation and stability of peptides
9. Absence of competing side reactions that could deplete the amino acid pool
10. Recycling mechanisms to regenerate hydrolyzed amino acids

These requirements must coexist in a prebiotic environment, presenting a formidable challenge to naturalistic explanations. Several of these conditions are mutually exclusive or contradictory. For instance, the need for water removal (point 6) conflicts with the aqueous environment typically assumed in prebiotic scenarios. Similarly, the pH conditions favorable for peptide bond formation (point 7) are not optimal for peptide stability.

The challenges are illustrated by the "alanine problem." Alanine, one of the simplest amino acids, forms peptides extremely slowly in aqueous solutions. Experiments have shown that at 25°C and pH 7, the equilibrium concentration of the alanine dipeptide is only about 10^-4 M when starting from a 1 M solution of alanine (Danger et al., 2012). This low yield highlights the thermodynamic barriers to even the simplest peptide formations.

Moreover, the requirement for energy input (point 1) often leads to increased rates of side reactions and decomposition, conflicting with the need for selective polymerization (point 5) and protection against hydrolysis (point 3).

The thermodynamic and kinetic barriers to prebiotic polypeptide formation present substantial challenges to current naturalistic explanations for the origin of life. Future discussions on this topic should focus on:

1. Developing more realistic models that account for both thermodynamic and kinetic constraints.
2. Investigating potential energy coupling mechanisms that could drive peptide bond formation.
3. Exploring non-aqueous environments or specialized micro-environments that might facilitate peptide formation and stability.
4. Addressing the mutual exclusivity of certain required conditions in prebiotic scenarios.
5. Critically examining the assumptions underlying current abiogenesis hypotheses in light of these fundamental chemical principles.

By rigorously addressing these points, the scientific community can work towards a more comprehensive and evidence-based understanding of the chemical processes that could have led to the emergence of the first polypeptides and, ultimately, life itself.

3.2 Chirality Issues

The challenges in achieving homochirality in prebiotic scenarios are multifaceted. The Soai reaction, known for chirality amplification, faces limitations due to the unlikelihood of abundant specific organic compounds on early Earth [24]. Varying racemization rates of amino acids, accelerated by metal ions like Cu(II), further complicate maintaining homochirality [20] [21]. Solid-state racemization of amino acids, even without water, persists at slower rates [23]. Kinetic resolution and asymmetric adsorption struggle to generate significant enantiomeric excess [20] ^[Context_6]. Circularly polarized light effects are wavelength-dependent and may cancel out in a prebiotic setting ^[Context_7]. The small energy difference between enantiomers is insufficient for spontaneous enrichment ^[Context_8]. Polymerization kinetics and cross-inhibition phenomena pose additional challenges ^[Context_9] ^[Context_10]. Addressing these complexities collectively in comprehensive models is crucial for advancing our understanding of homochirality in the origin of life research.

1. Amplification of Chirality
The Soai reaction, often cited as a potential mechanism for chirality amplification, faces significant hurdles in prebiotic contexts. This autocatalytic reaction, while demonstrating impressive enantiomeric excess amplification in laboratory settings, requires specific organic compounds (like pyrimidine-5-carbaldehydes) that are unlikely to have been present in significant quantities on the early Earth.

2. Racemization Rates of Different Amino Acids
Different amino acids racemize at varying rates, further complicating the maintenance of homochirality. For instance, aspartic acid racemizes relatively quickly, while isoleucine is more resistant to racemization. This differential racemization would lead to a non-uniform loss of homochirality across a peptide chain, potentially disrupting any functional structures that might have formed.

3. Impact of Metal Ions
The presence of metal ions, which would have been common in prebiotic environments, can significantly accelerate racemization rates. For example, Cu(II) ions have been shown to increase the rate of aspartic acid racemization by a factor of 10^4 at pH 7.4 and 37°C.

4. Racemization in Solid State
Even in the absence of water, amino acids can undergo solid-state racemization, albeit at slower rates. This implies that even if a mechanism for removing water was present, it would not completely halt the racemization process.

5. Kinetic Resolution
While kinetic resolution through selective crystallization has been proposed as a mechanism for generating enantiomeric excess, it faces significant challenges in prebiotic scenarios. The process requires specific conditions and often results in the loss of a significant portion of the material.

6. Asymmetric Adsorption
The idea that chiral surfaces could selectively adsorb one enantiomer over another has been explored, but the effect is generally too weak to generate significant enantiomeric excess. Moreover, the adsorbed molecules would need to be released to participate in further reactions, negating any accumulated excess.

7. Photochemical Reactions
While circularly polarized light can induce small enantiomeric excesses, the effect is wavelength-dependent and can produce opposite results at different wavelengths. In a prebiotic setting with broad-spectrum light, these effects would likely cancel out.

8. Thermodynamic Considerations
The difference in Gibbs free energy between enantiomers due to parity violation is extremely small (estimated at 10^-11 J/mol for alanine). This difference is insufficient to drive spontaneous enantiomeric enrichment under prebiotic conditions.

9. Polymerization Kinetics
Even if a slight enantiomeric excess were achieved, the kinetics of polymerization would need to strongly favor the excess enantiomer to produce homochiral polymers. Current models suggest that the required kinetic differences are unrealistically large for prebiotic scenarios.

10. Cross-Inhibition
In systems with multiple amino acids, the presence of the wrong enantiomer of one amino acid can inhibit the polymerization of the correct enantiomers of other amino acids, a phenomenon known as cross-inhibition. This further complicates the path to homochiral polymers in a mixed prebiotic environment.

These points further underscore the significant challenges faced by naturalistic explanations for the origin of biological homochirality. Future research in this field should focus on developing comprehensive models that address these multifaceted issues simultaneously, rather than tackling them in isolation. It's crucial to consider the interplay between various factors such as racemization rates, polymerization kinetics, and environmental conditions in prebiotic scenarios. Additionally, exploring potential non-aqueous environments or unique geological settings that might provide more favorable conditions for maintaining homochirality could offer new insights into this fundamental question in origin of life research.

The racemization of amino acids and polypeptides under natural conditions is inevitable

Dr. Royal Truman, an American scientist, and Dr. Boris Schmidtgall, a Russian / German scientist proposed recently a remarkable conclusion with potentially devastating consequences for the origin of life community: random polypeptide sequences in water always seem to racemize faster than chain elongation can occur.
Even beginning with short, random sequence polypeptides containing pure L-aa together with initially only pure L-aa in water, the rate of condensation
aa + [peptide]n-1  [peptide]n + H2O

always seems to be slower than racemization, at all temperatures, under unguided, natural conditions. This is a devastating discovery for the origin of life (OoL) community since it implies that only random L- and D-polypeptide sequences can develop naturally in water instead of L-only required for life.
The team published a series of remarkable papers on the racemization of amino acids in water as a function of temperature. Condensation and hydrolyzation of polypeptides are equilibrating processes (amino acid is abbreviated as aa):

aa + [peptide]n-1  [peptide]n + H2O

but simultaneously the aa residues of peptides also racemize. Chemists soon agreed that indeed racemization should always be faster than chain elongation since the former is an unimolecular reaction involving only the polypeptide whereas the second is bimolecular and involves the same low-concentration polypeptide but also requires an amino acid that is present in low concentrations. The relative rate constants and thermodynamics reinforced this conclusion.
 
A few highlights of their analysis of the best-known studies include these points:
1. Using generous estimates for prebiotic glycine concentrations (10^4 M), the equilibrium concentration of a 9-residue glycine peptide would be ≈ 5 × 10^51 M.
2. The formation of peptides in water is thermodynamically unfavorable, with hydrolysis being strongly favored over condensation. [Gly]n < [Gly]n-1 by a factor of about 2 × 10^6 for every length n. At equilibrium, negligible amounts of larger polypeptides can exist.
3. Elongation and L to D inversion occur primarily at the peptide end residues, simplifying the analysis.
4. To form a detectable amount of even very small peptides the experiments always had to use unrealistically high amino acid concentrations and experimental conditions.
5. Experiments in clays, minerals, at air-water interfaces, etc., despite optimized lab conditions produced very low amounts of small oligopeptides.
6. Experiments using high temperatures and pressures to simulate hydrothermal vents temporarily produced only small amounts of oligopeptides up to 8 residues long and then rapidly decomposed chemically.
7. Experiments using artificially activated amino acids and specific conditions in laboratories to force peptide formation have no relevance to abiogenesis.
8. The largest peptides produced under optimized (prebiotically irrelevant) laboratory conditions without catalysts were around 12-14 glycine residues, with possible traces of up to 20 residues. Left in water these would have hydrolyzed.
9. Even under ideal conditions, a small percentage of D-amino acids would prevent L-polypeptides from forming stable secondary structures in water.
10. Formation of secondary structures using designed sequences that hinder racemization is not plausible given the relative distribution of aa and would be too rare to be relevant for OoL purposes.
11. Assumed racemization rate constants are often adjusted for archeological purposes to match preconceived dates rather than questioning those dates.
12. Factors like temperature, pH, mineralization, hydrolysis, and contamination can all significantly impact racemization rates for archeological purposes.
13. Laboratory methods for amplifying small enantiomeric excesses face limitations:
- Partial sublimation of enantiomers would destroy most of the material and simply remix.
- Crystal separation techniques require specific and unlikely natural conditions.
- Separation of the eutectic mixture leads to remixing in water afterward.
- Chiral minerals produce small excesses, but they exist equally in D- and L- forms.
- Chiral or auxiliary catalysts require unrealistic concentrations and produce opposing results depending on the amino acid used.
14. Parity violation and circularly polarized light can only produce minimal enantiomeric excesses, too small for the purposes of abiogenesis.



Last edited by Otangelo on Tue Jul 09, 2024 11:34 am; edited 4 times in total

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3.3 Sequence and Structure Formation in Prebiotic Protein Evolution: A Critical Analysis

This analysis examines the challenges of sequence and structure formation in prebiotic protein evolution, focusing on the improbabilities and contradictions inherent in current naturalistic explanations. The challenges of sequence and structure formation in prebiotic protein evolution, as highlighted in recent research, underscore the improbabilities inherent in naturalistic explanations. Calculations show that even with flexibility in protein sequences, the probability of randomly generating a functional protein is astronomically low, emphasizing the need for efficient mechanisms to bias sequence space towards functionality [24]. These challenges cast doubt on the plausibility of random assembly models for protein origin, given the vanishingly small probability of forming even one functional protein sequence within Earth's history [25]. The requirements for natural protein formation, such as amino acid availability, peptide bond formation, and chiral selectivity, must be met simultaneously under prebiotic conditions, posing significant contradictions and mutually exclusive conditions [26]. Current models often rely on unspecified self-organizing principles, necessitating future research to quantify probabilities rigorously, propose testable mechanisms, and explore alternative models to advance our understanding of biological complexity origins [27].

1. Quantitative Challenges

The probability of forming a functional protein sequence by chance is astronomically low. Consider a relatively short protein of 150 amino acids:

- There are 20 standard amino acids.
- The number of possible sequences is 20^150 ≈ 10^195.

Not all positions in a protein sequence need to be strictly specified for the protein to be functional. This is an important consideration that can significantly affect the probability calculations.  For this calculation, let's consider a hypothetical enzyme of 150 amino acids and make some reasonable assumptions:

1. Active site residues: Let's say 5 residues are critical for the catalytic function and must be exactly specified.
2. Substrate binding pocket: Perhaps 10 residues are important for substrate recognition and binding, but some variation is allowed. Let's say each of these positions can tolerate 5 different amino acids on average.
3. Structural integrity: Maybe 30 residues are important for maintaining the overall fold, but have some flexibility. Let's assume each of these can be any of 10 different amino acids.
4. The remaining 105 residues can be any amino acid, as long as they don't disrupt the structure (let's assume all 20 are allowed).

Now, let's calculate:

1. Active site: 20^5 possibilities (must be exact)
2. Binding pocket: 5^10 possibilities (5 options for each of 10 positions)
3. Structural residues: 10^30 possibilities
4. Remaining residues: 20^105 possibilities

Total number of possible functional sequences: 20^5 * 5^10 * 10^30 * 20^105 ≈ 3.2 * 10^158. Compare this to the total number of possible sequences: 20^150 ≈ 1.4 * 10^195. Probability of randomly generating a functional sequence: (3.2 * 10^158) / (1.4 * 10^195) ≈ 2.3 * 10^-37 or about 1 in 4.3 * 10^36.  To put it in perspective:

- If we could test 1 trillion (10^12) sequences per second
- And we had been doing so since the beginning of the universe (about 13.8 billion years or 4.4 * 10^17 seconds)
- We would have only tested about 4.4 * 10^29 sequences

This is still about 10 million times fewer than the number we'd need to test to have a good chance of finding a functional sequence.

These calculations demonstrate that even when we account for the flexibility in protein sequences, the probability of randomly generating a functional protein remains extremely low. This underscores the challenge faced by naturalistic explanations for the origin of proteins and emphasizes the need for mechanisms that can efficiently search or bias the sequence space towards functional proteins.

2. Implications for Current Models

These calculations severely challenge the plausibility of random assembly models for protein origin. Even considering the entire history of Earth (≈4.5 billion years) and assuming extremely rapid amino acid combinations (e.g., 1 trillion per second), the probability of forming even one functional protein sequence remains vanishingly small.

3. Requirements for Natural Protein Formation

1) Availability of all 20 standard amino acids in sufficient concentrations
2) A mechanism for amino acid activation (to overcome thermodynamic barriers)
3) A way to form peptide bonds in an aqueous environment
4) Protection from hydrolysis once peptide bonds form
5) A mechanism for sequence selection or amplification of functional sequences
6) Prevention of cross-reactions with other prebiotic molecules
7) A process for maintaining chirality (all L-amino acids)
8 ) A method for achieving proper folding in the absence of chaperone proteins
9) Removal of non-functional or misfolded proteins
10) A system for replicating successful sequences

4. Simultaneous Fulfillment Under Prebiotic Conditions

These requirements must all be met concurrently in a prebiotic environment lacking biological machinery. This presents a formidable challenge, as many of these conditions are mutually exclusive or require sophisticated mechanisms that are themselves products of evolution.

5. Contradictions and Mutually Exclusive Conditions

- Requirement 3 (peptide bond formation in water) contradicts requirement 4 (protection from hydrolysis).
- The need for concentration of amino acids (1) conflicts with the dilute conditions of prebiotic oceans.
- Maintaining chirality (7) is at odds with the racemization that occurs naturally in aqueous environments.

6. Scientific Terminology

Key concepts include:
- Peptide bond formation
- Hydrolysis
- Racemization
- Chiral selectivity
- Protein folding
- Primary, secondary, tertiary, and quaternary structure
- Levinthal's paradox

7. Illustrative Scenario

Consider the formation of a simple enzyme like ribonuclease, with 124 amino acids. In a prebiotic ocean, amino acids would need to:
1. Concentrate sufficiently
2. Activate (overcoming thermodynamic barriers)
3. Form correct peptide bonds in sequence
4. Avoid hydrolysis
5. Maintain homochirality
6. Fold correctly without chaperones
7. Achieve catalytic activity

The improbability of this occurring by chance is compounded by the fact that ribonuclease itself is not self-replicating, so the process would need to repeat independently.

8. Critical Examination

Current models often rely on unspecified "self-organizing principles" or "emergent properties" to bridge the gap between simple chemicals and functional proteins. However, these concepts lack concrete mechanisms and often amount to restatements of the problem rather than solutions.

9. Conclusion and Future Discussions

Future discussions on protein origins should:
1. Quantify probabilities rigorously
2. Address each requirement explicitly
3. Propose testable mechanisms for overcoming statistical improbabilities
4. Consider alternative models that do not rely solely on chance assembly
5. Explore potential non-aqueous environments or unique geological settings
6. Investigate the minimal functional requirements for proto-proteins

By structuring the debate around these points, we can more accurately assess the viability of current theories and guide future research into the origins of biological complexity.

3.4  Scale and Reproduction in Prebiotic Systems: A Critical Analysis

The challenges of achieving scale and reproduction in prebiotic systems are highlighted by the quantitative analysis of the probability of randomly assembling a specific genome, exemplified by Pelagibacter ubique, one of the smallest free-living organisms with a genome size of ~1,300,000 base pairs. The calculated probability of (1/4)^1,300,000 ≈ 10^-782,831 underscores the immense improbability of spontaneously generating such a genome. This probability is significantly smaller than the number of atoms in the observable universe or the microseconds since the Big Bang, emphasizing the astronomical odds against the random assembly of a functional genome. Even with every atom representing a unique DNA sequence and checking a trillion sequences per microsecond since the universe's inception, the number of sequences checked would be minuscule compared to the vast search space required, illustrating the formidable obstacles faced by naturalistic explanations for the origin of life.

1. Quantitative Challenges

Consider the requirements for a minimal self-replicating system: 

Calculation of Genome Probability for a Minimal Free-Living Organism

While Mycoplasma genitalium is often cited for its small genome, it's crucial to note that it's an endosymbiont and parasite, relying on its host for many essential nutrients and functions. Therefore, it's not an adequate example of a minimal free-living organism. A more appropriate example is Pelagibacter ubique, one of the smallest known free-living organisms. Let's use this for our calculation:

1. Genome size of Pelagibacter ubique: ~1,300,000 base pairs
2. Each position can be one of 4 nucleotides (A, T, C, G)

Probability of randomly assembling this specific genome: (1/4)^1,300,000 ≈ 10^-782,831

To put this number in perspective:

- Number of atoms in the observable universe: ~10^80
- Number of microseconds since the Big Bang: ~4.3 x 10^23

The probability we calculated is vastly smaller than either of these numbers. Even if every atom in the universe represented a unique DNA sequence, and we could check a trillion (10^12) sequences every microsecond since the beginning of the universe, we would have only checked: 10^80 * 4.3 x 10^23 * 10^12 ≈ 4.3 x 10^115 sequences. This is nowhere near the 10^782,831 sequences we would need to check to have a reasonable chance of finding our target genome.

Implications:

1. This calculation, based on a true free-living organism, underscores the astronomical improbability of a functional genome arising by chance.
2. It highlights the need for alternative explanations that don't rely on pure chance, such as:
   - Chemical evolution with selection pressures
   - Self-organizing principles in complex chemical systems
   - Potential for simpler initial self-replicating systems

3. It emphasizes the vast gulf between simple chemical systems and even the simplest known free-living systems, challenging gradualist explanations for the origin of life.
4. This calculation reinforces the need for a more comprehensive understanding of how functional biological information can arise from prebiotic chemistry.
5. It illustrates why using parasitic or endosymbiotic organisms as examples can be misleading when discussing minimal genome sizes for free-living organisms.

These numbers, based on a more appropriate example of a minimal free-living organism, illustrate why the origin of life remains one of the most challenging questions in science. They underscore the significant hurdles faced by current naturalistic explanations in accounting for the emergence of complex, self-replicating systems capable of independent existence. Even if every atom in the universe represented a unique DNA sequence, the probability of randomly generating a minimal genome remains vanishingly small.

2. Implications for Current Models

These calculations severely challenge the plausibility of random assembly models for the origin of self-replicating systems. The vast sequence space that must be explored to find functional genomes is incompatible with the time and resources available in prebiotic Earth scenarios.

3. Requirements for Natural Scale and Reproduction

1. A mechanism for producing large numbers of identical molecular components
2. A system for accurate information storage and transfer (e.g., nucleic acids)
3. A means of translating stored information into functional molecules (e.g., proteins)
4. An energy harvesting and utilization system
5. A boundary system (e.g., membrane) to contain and protect components
6. A mechanism for the growth and division of the boundary system
7. A way to coordinate replication of internal components with boundary division
8. A system for error detection and correction during replication
9. A means of adapting to environmental changes
10. A transition mechanism from prebiotic chemistry to cellular biochemistry

4. Simultaneous Fulfillment Under Prebiotic Conditions

These requirements must all be met concurrently in a prebiotic environment lacking biological machinery. This presents a formidable challenge, as many of these conditions require sophisticated mechanisms that are themselves products of evolution.

5. Contradictions and Mutually Exclusive Conditions

- The need for a protective boundary (5) conflicts with the requirement for nutrient influx and waste removal.
- Accurate replication (8 ) requires complex enzymatic machinery, which itself requires accurate replication to exist.
- The transition from prebiotic to cellular synthesis (10) requires a system that can function in both regimes simultaneously.

6. Scientific Terminology

Key concepts include:
- Genome
- Self-replication
- Translation
- Transcription
- Metabolism
- Lipid bilayers
- Error catastrophe
- Autocatalysis
- Ribozymes
- Protocells

7. Illustrative Scenario

Consider the formation of a primitive protocell:
1. Lipids must spontaneously form a stable vesicle
2. Replicating RNA molecules must be encapsulated
3. The RNA must code for and produce functional peptides
4. These peptides must assist in RNA replication and vesicle growth
5. The system must divide, distributing components to daughter cells
6. This process must occur repeatedly without loss of function

The coordinated emergence of these features in a prebiotic setting strains the explanatory power of current naturalistic models.

8. Critical Examination

Current models often invoke "self-organization" or "emergent complexity" to bridge the gap between simple chemical systems and self-replicating protocells. However, these concepts lack specificity and often amount to restatements of the problem rather than solutions. The transition from non-living to living systems represents a staggering increase in functional information content, which is not adequately explained by known physical or chemical principles.

9. Conclusion and Future Discussions

Future discussions on the origin of self-replicating systems should:
1. Quantify the minimal functional requirements for self-replication rigorously
2. Address each requirement explicitly, providing plausible prebiotic mechanisms
3. Propose testable hypotheses for the coordinated emergence of replication, metabolism, and containment
4. Consider alternative models that do not rely solely on chance assembly or gradual accumulation of features
5. Investigate potential non-aqueous environments or unique geological settings that might facilitate more rapid exploration of chemical space
6. Explore the concept of "functional information" and its origins in prebiotic systems

By structuring the debate around these points, we can more accurately assess the viability of current theories and guide future research into the origins of biological complexity. The field must grapple with the enormous gulf between simple chemical reactions and the sophisticated, information-rich systems characteristic of even the simplest known life forms.

3.5 Amplification of Enantiomeric Excess

The amplification of enantiomeric excess (ee) from a small initial value to 100% L-amino acids has been a topic of extensive research and debate. Literature experiments have not supported the idea that small excesses of L-amino acids can be amplified to complete homochirality, with proposed mechanisms often requiring unrealistic experimental conditions. Studies have explored various scenarios like partial sublimation, crystal separation, and chiral catalysts but have faced significant limitations in achieving and maintaining high ee values. Research has shown that natural processes alone may not be sufficient to drive the amplification of ee to complete homochirality, highlighting the complexity of this phenomenon [1] [2] [3] [4] [5].

Literature experiments do not corroborate that a small excess of L-amino acid could be amplified to form 100% L-amino acids 

In a series of remarkable papers, senior chemists from several firms, Dr. Royal Truman, Dr. Chris Basel, and Dr. Stephen Grocott did an extensive analysis of the key literature on amplification experiments of small excesses of L-amino acids. The evolutionary experiments reviewed had been designed to find special conditions to preferentially extract excess L-amino acids from mixtures and separate a portion having a higher proportion of L-amino acid (aa).
Their conclusions are very bad news for the origin of life (OoL) community, demonstrating that implausible experimental conditions had to be used. Objective evaluation of the results showed that the attempts to find relevant amplification scenarios had failed badly.
To illustrate, a hypothetical astronomical source of right-circularly polarized UV light (r-CPL) is the preferred evolutionary theory for the origin of homochiral amino acids. However, astronomers have been unable to find polarized UV light anywhere in the relevant region of space.
We encourage you to read the papers covering the topics of interest. Here are some bullet points extracted from this series of papers.
 
1. Claims of significant enantiomeric excess produced by a hypothetical astronomical  circularly polarized light (CPL) source are misleading:
- Astronomers have not found polarized UV light in a relevant region of space
- The theory required very specific conditions and laboratory conditions untypical in space
- The theory requires almost 100% photodestruction of all amino acids before an excess could result (but 100% destruction would serve no purpose!).
2. Different amino acids absorb left-handed and right-handed CPL differently at various UV wavelengths. Therefore, the expected result would be an averaging out with little or no survival of one enantiomer.
3. Experimental approaches focused on the very exceptional amino acids with the highest anisotropy factors and used optimal wavelengths designed to produce the researcher’s goal instead of real-world outcomes.
4. Even if a small enantiomeric excess were produced in space, it would likely be further diluted upon reaching Earth.
5. The major literature examples like alkylation of Soai and polymerization of cyclobutene have no relevant to OoL. In many cases such as selective adsorption on minerals such as kaolinite and montmorillonite clay even the irrelevant examples published have been disproven when the experiments were repeated.
6. Adsorption on chiral calcite and quartz would produce equal amounts of D and L enantiomers overall.
7. Extracting only L-amino acids from glycine crystals required pure D-leucine, an unlikely natural scenario.
8. The formation of enantiomer-specific crystalline islands required laboratory processes not found in nature.
9. There is no credible reason why enantiomers of separate amino acids would not remix in natural environments.
10. Any enantiomeric excess produced would racemize in water over time.
11. Proposed mechanisms required carefully planned and executed laboratory conditions that are unlikely in nature.
12. None of the proposals known could have occurred naturally without intelligent guidance.
13. Different amino acid precursors behave differently with the same sugar catalysts, making it impossible to generalize about sugar-induced chirality.
14. The used D-lyxose to favor production of L-amino acids did not occur when tested using alanine.
15. On longer time scales relevant to prebiotic scenarios, racemic mixtures would result regardless of the initial sugar-induced excess.
16. Impurities have been tested to enhance the crystallization of a particular enantiomer.
- This only produced conglomerate crystals, but not separated enantiomers.
- The supersaturated pure solutions used to form crystals used would not have exist naturally.
- Conditions to favor one L-amino acid would have increased the amount of D- enantiomer of other amino acids, making matters worse for OoL purposes.
17. Excess of non-biological L-α-methyl amino acids have been claimed in meteorites. Experiments showed that mixing L-α-methylamine with racemic L- and D amino acid produced more of the wrong D- amino acids. Even had the desired outcome been obtained, equilibration L  D occurred rapidly, especially at elevated temperature.
18. Extensive experiments with L-α-methyl amino acids and many catalyst showed the desired outcome when using copper but at plausible concentrations the enantiomeric effect was negligible and racemization would have occurred in the presence of such a catalyst rapidly.
19. Simulations of wet-dry cycles with L-amino acids and L-isovaline in montmorillonite clay:
- Led to rapid racemization of amino acids, very bad news for OoL purposes.
- Showed that chirality could not be effectively transferred from L-isovaline to produce L-amino acids.
20. Instant sublimation experiments at ~ (430°C) followed by instant cooling at sub-freezing temperatures (!?) to avoid thermal degradation experiments have no relevance for OoL purposes: aa degrade at much lower temperatures.
21. Sublimation experiments using serine relied on unrealistic, optimized laboratory conditions (and did not work with other aa):
- High temperatures around exactly 205°C with short heating times (2-18 hours)
- Rapid cooling with dry ice and N2 gas flow to quickly remove sublimate
- Avoiding serine racemization and decomposition at high temperatures.
- The maximum enantiomeric excess achieved was too low for biological purposes.
Worse, starting with an L-enantiomeric excess of serine actually produced a sublimate with a lower excess!
22. Sublimation experiments using mixtures of Asn, Thr, Asp, Glu, and Ser cleverly mixed with volatile racemic Ala, Leu, Pro, or Val required carefully optimized laboratory conditions to obtained the intended goal:
- Low pressure (0.3-0.7 mbar) , controlled temperature (100-105°C)  and duration of 14 hours
- Use pure L enantiomers, and prevent remixing of sublimate and residue
- Use of an icy cold finger to trap the sublimate.
The results were less than encouraging. Using L-enantiomers of the less sublimated aa produced sublimates enriched in D-enantiomers of the volatile aa, the opposite needed for biology!
23. Only two biological amino acids (threonine and asparagine) naturally crystallize as conglomerates of distinct D and L crystals, but under conditions not relevant for OoL.
24. Most biological aa form racemic crystals (equal amounts of D and L enantiomers) preventing crystalline excesses. Any excess in solution would simply racemize over time.
25. Random temperature variation would prevent the precise control needed to take advantage of the eutectic point for some aa to separate crystals with an excess of an enantiomer.
26. Laboratory conditions were used to extract enantiomer excesses already present, including saturated solutions of a pure aa, controlled temperatures, and constant agitation.
27. Natural processes such as rainwater, seawater, and groundwater would have diluted any enantiomeric excess and led to remixing.
28. If hypothetically an excess would exist in solution that could crystallize preferentially into L-crystals, eventually the excess would be depleted and all the aa would then crystallize out of solution, contamination the first batches.
29. In any scenario of excess in liquid or crystal phase remixing would occur, racemization over time, and contamination with racemic mixtures in the environments.
30. Some experiments used complex catalysts not found naturally to increase racemization, of the wrong D-amino acids but they would have also racemized all the L-amino acids indiscriminately.
31. Techniques like Preferential Enrichment and CIAT rely on an initial excess of L-enantiomer, organic solvents like aspartic acid and acetic acid, and typically salicylaldehyde as catalyst at 90-160°C with agitation in a special container. None of these are relevant for OoL purposes.
Here are some additional points to complement the existing information on challenges to amplifying small excesses of L-amino acids to form 100% L-amino acids:
32. Attempts to use chiral minerals like quartz as selective catalysts have shown only very small enantiomeric excesses, typically less than 1%.
33. Proposed autocatalytic reactions like the Soai reaction require highly specific precursor molecules and conditions not plausible in prebiotic environments.
34. Theoretical models of amplification often rely on unrealistic assumptions about reaction kinetics and equilibrium conditions.
35. Experiments using temperature gradients to separate enantiomers produce only transient and localized excesses that quickly dissipate.
36. Proposed mechanisms involving chiral light or spin-polarized electrons lack a demonstrated source in early Earth environments.
37. Attempts to use amino acid precursors like α-methyl amino acids as chiral catalysts have shown limited effectiveness and selectivity.
38. Proposed amplification via polymerization faces issues of reversibility and lack of selectivity for homochiral products.
39. Scenarios involving partial crystallization require precise control of supersaturation, nucleation, and growth conditions unlikely in nature.
40. Attempts to exploit slight solubility differences between enantiomers have produced only marginal enrichment.
41. Proposed chiral amplification via asymmetric autocatalysis faces issues of product inhibition and side reactions.

The overall picture reinforces the significant hurdles facing naturalistic explanations for the origin of biological homochirality.

4. Additional Considerations

4.1 Optimal Set of Amino Acids

Recent studies by Philip and Freeland (2011) and Ilardo et al. (2015) have highlighted the exceptional optimality of the standard 20 amino acid alphabet in life, showcasing high coverage of crucial chemical properties like size, charge, and hydrophobicity that outperform vast alternative alphabets. These findings challenge conventional theories of chemical evolution, indicating a level of selection or foresight that contradicts undirected processes. To naturally achieve such an optimal amino acid set, prebiotic conditions must simultaneously provide a diverse amino acid pool, a sophisticated selection mechanism, discernment of subtle chemical differences, balance simplicity with functional diversity, compatibility with translation machinery, stability under prebiotic conditions, reactivity for peptide bond formation, and rapid selection before other biochemical systems emerge, presenting significant contradictions in the origin of life hypotheses [1] [2].

1. Quantitative Findings Challenging Conventional Theories

A study by Philip and Freeland (2011) compared the standard 20 amino acid alphabet to random sets of amino acids chosen from a larger pool of 50 plausible prebiotic amino acids. They found that the standard alphabet exhibits unusually high coverage of three key chemical properties: size, charge, and hydrophobicity. Out of 10^19 possible alternative alphabets, only one in a million matched or exceeded the standard alphabet's coverage of these properties.

Another study by Ilardo et al. (2015) used a computational model to assess the designability and folding stability of proteins made from various amino acid alphabets. They found that the standard 20 amino acid set outperformed most alternative sets, including those with more amino acids, in producing stable, well-folded proteins.

2. Implications for Current Scientific Models

These findings pose significant challenges to current models of chemical evolution. Conventional theories typically assume that the set of amino acids used in life was determined by availability in the prebiotic environment or by chance. However, the observed optimality suggests a level of "foresight" or selection that is difficult to reconcile with undirected processes.

3. Requirements and Conditions

For the optimal set of amino acids to arise naturally, the following conditions must be met simultaneously under prebiotic conditions:

1. A diverse pool of amino acids must be available in the prebiotic environment.
2. A mechanism must exist to select amino acids based on their functional properties rather than just their abundance.
3. The selection process must be able to distinguish between subtle differences in chemical properties among similar amino acids.
4. The chosen set must provide a balance between simplicity (fewer amino acids) and functional diversity.
5. The selection process must occur before the establishment of the genetic code, as the code itself would constrain further changes to the amino acid alphabet.
6. The selected set must be compatible with the emerging translation machinery, including tRNA and aminoacyl-tRNA synthetases.
7. The chosen amino acids must be stable under prebiotic conditions yet reactive enough to form peptide bonds.
8. The selection process must occur rapidly enough to establish the optimal set before other, potentially incompatible biochemical systems emerge.

These requirements present several contradictions:
- The need for a diverse initial pool conflicts with the selective pressures that would limit the variety of compounds produced abiotically.
- The requirement for a sophisticated selection mechanism conflicts with the presumed simplicity of prebiotic chemical systems.
- The need for rapid selection conflicts with the gradual nature of evolutionary processes.

4. Relevant Scientific Terminology

Proteinogenic amino acids, chemical evolution, prebiotic chemistry, abiogenesis, protein folding, hydrophobicity, designability, genetic code, tRNA, aminoacyl-tRNA synthetases, peptide bond formation.

5. Illustrative Examples

Consider the case of lysine and arginine, two positively charged amino acids in the standard set. Both could plausibly form in prebiotic conditions, but arginine is more complex and less likely to arise spontaneously. However, arginine's guanidinium group provides unique properties for protein function. A purely abundance-based selection would likely have chosen lysine alone, missing the functional advantages of including both.

6. Critical Examination of Current Theories

Current theories of chemical evolution struggle to explain the observed optimality of the amino acid alphabet. Models based on prebiotic availability fail to account for the inclusion of less common amino acids like tryptophan or the exclusion of simpler, more abundant ones like norvaline. Scenarios invoking serial selection of amino acids face the challenge of explaining how early choices could anticipate future functional needs.

7. Further Discussion

Future discussions on this topic should focus on developing testable hypotheses that can explain the apparent optimality of the amino acid set without invoking teleological mechanisms. This might include exploring potential feedback loops between amino acid availability and early metabolic cycles, or investigating whether alternative optimal sets exist that might have been discoverable through plausible chemical evolution scenarios. In conclusion, the near-optimal nature of the 20 proteinogenic amino acids presents a significant challenge to naturalistic explanations for the origin of life. While not insurmountable, this challenge requires careful consideration and may necessitate revisions to current models of chemical evolution and abiogenesis.



Last edited by Otangelo on Tue Jul 09, 2024 11:35 am; edited 6 times in total

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4.2 Protein Folding and Chaperones

Recent studies highlight that a substantial portion of newly synthesized proteins in eukaryotic and prokaryotic cells rely on molecular chaperones for proper folding, challenging conventional theories of early protein evolution . The intricate process of protein folding, with vast conformational possibilities, occurs rapidly due to the energy landscape and chaperone assistance. These findings raise significant questions about the evolution of functional proteins without pre-existing chaperone systems, presenting a "chicken and egg" dilemma. Early protein evolution faces contradictions regarding the necessity of complex regulatory mechanisms, specific environmental conditions, and the availability of energy sources for chaperone-assisted folding. The GroEL/GroES chaperonin system exemplifies the complexity of chaperones, challenging the idea of their evolution in the absence of functional proteins. Addressing these challenges requires exploring primitive folding mechanisms and potential evolutionary starting points for protein folds, urging a reevaluation of current models of early protein evolution [35].

1. Quantitative Findings Challenging Conventional Theories

Recent studies have shown that approximately 30-50% of newly synthesized proteins in eukaryotic cells require assistance from molecular chaperones to achieve their native, functional states (Balchin et al., 2016). In prokaryotes, this percentage is lower but still significant, with about 10-20% of proteins needing chaperone assistance (Hartl et al., 2011).

The folding process itself is extremely complex. For a small protein of 100 amino acids, there are approximately 10^30 possible conformations. Yet, proteins typically fold into their native states on timescales of milliseconds to seconds (Dill and MacCallum, 2012). This speed is possible only because of the energy landscape of protein folding and the assistance of chaperones.

2. Implications for Current Scientific Models

These findings pose significant challenges to current models of early protein evolution. The high percentage of proteins requiring chaperones for proper folding suggests that early functional proteins would have faced severe limitations without a pre-existing chaperone system. This creates a "chicken and egg" problem: how could complex, functional proteins evolve if they required equally complex chaperone systems to fold correctly?

3. Requirements and Conditions

For early proteins to fold correctly and function in a prebiotic environment, the following conditions must be met simultaneously:

1. Amino acids must spontaneously form peptide bonds in the correct sequence.
2. The resulting polypeptides must be able to fold into stable, functional conformations.
3. The prebiotic environment must provide conditions conducive to protein folding (appropriate pH, temperature, and ionic concentrations).
4. Mechanisms must exist to prevent protein aggregation and misfolding.
5. For proteins requiring chaperones, a primitive chaperone system must already be in place.
6. This primitive chaperone system must itself be composed of properly folded proteins.
7. Energy sources (e.g., ATP) must be available to power chaperone-assisted folding.
8. Feedback mechanisms must exist to regulate chaperone activity and prevent over-assistance.
9. A system must be in place to degrade misfolded proteins that escape chaperone assistance.

These requirements present several contradictions:
- The need for a pre-existing chaperone system conflicts with the assumption that early proteins evolved in its absence.
- The requirement for complex regulatory mechanisms contradicts the presumed simplicity of early biological systems.
- The need for specific environmental conditions conflicts with the variable and often extreme conditions of the prebiotic Earth.

4. Relevant Scientific Terminology

Protein folding, molecular chaperones, native state, energy landscape, aggregation, misfolding, ATP-dependent chaperones, chaperonins, heat shock proteins (HSPs), protein quality control, proteostasis.

5. Illustrative Examples

Consider the GroEL/GroES chaperonin system in E. coli. This complex molecular machine encapsulates unfolded proteins in a hydrophilic chamber, allowing them to fold without interference. The system requires 14 identical 57 kDa GroEL subunits and 7 identical 10 kDa GroES subunits, arranged in a highly specific structure. It's challenging to envision how such a complex system could have evolved in the absence of already functional proteins.

6. Critical Examination of Current Theories

Current theories of early protein evolution often overlook or underestimate the challenges posed by protein folding. Models that propose the gradual evolution of protein function fail to account for the complex folding requirements of even relatively simple proteins. Scenarios invoking short peptides as early functional molecules face the challenge of explaining how these could have evolved into complex, chaperone-dependent proteins.

The RNA World hypothesis, which proposes RNA as the original self-replicating molecule, also faces challenges in explaining the transition to a protein-based metabolism. The complexity of the translation machinery and the need for already-folded proteins in this process create significant hurdles for this model.

7. Suggestion for Further Discussion

Future discussions on this topic should focus on developing testable hypotheses for primitive folding mechanisms that could have operated in the absence of modern chaperone systems. This might include exploring the potential role of mineral surfaces or simple organic molecules in facilitating early protein folding, or investigating whether certain protein folds are inherently more likely to form spontaneously and could have served as evolutionary starting points. In conclusion, the complexity of protein folding and the widespread requirement for chaperones in modern cells present significant challenges to naturalistic explanations for the origin of life. These challenges necessitate a reevaluation of current models and may require new, innovative approaches to understanding early protein evolution.

4.3 Metabolic Integration

The integration of synthesized proteins into functional metabolic pathways presents significant challenges to current naturalistic explanations for the origin of life. This analysis will focus on the complexities of metabolic integration, particularly in the context of amino acid biosynthesis, and the implications for early cellular evolution.

1. Quantitative Findings Challenging Conventional Theories

Recent studies have shown that a minimum of 112 enzymes is required to synthesize the 20 standard proteinogenic amino acids plus selenocysteine and pyrrolysine (Fujishima et al., 2018). This number represents a significant increase from earlier estimates and highlights the complexity of even the most basic cellular metabolic processes. Furthermore, these 112 enzymes are involved in a network of interdependent reactions. A study by Ravasz et al. (2002) on the metabolic network of E. coli revealed a hierarchical organization with a scale-free topology, characterized by a few highly connected metabolic hubs. This structure implies that the removal of even a small number of key enzymes could lead to catastrophic system-wide failures.

2. Implications for Current Scientific Models

These findings pose significant challenges to current models of early cellular evolution. The high number of enzymes required for amino acid biosynthesis suggests that early cells would have needed a remarkably complex metabolic system from the outset. This complexity is difficult to reconcile with the idea of a gradual evolution of metabolic pathways from simpler precursors. The interdependence of these enzymes also creates a "chicken and egg" problem: how could such a complex system of protein-based enzymes evolve when proteins themselves require this system to be synthesized?

3. Requirements and Conditions

For metabolic integration to occur naturally in a prebiotic environment, the following conditions must be met simultaneously:

1. A diverse pool of amino acids must be available in sufficient quantities.
2. Mechanisms for forming peptide bonds must exist to create functional enzymes.
3. Each of the 112+ enzymes required for amino acid biosynthesis must be present and functional.
4. These enzymes must be produced in the correct ratios to maintain metabolic balance.
5. Cofactors and coenzymes necessary for enzyme function must be available.
6. Energy sources (e.g., ATP) must be present to drive unfavorable reactions.
7. Cellular compartmentalization must exist to concentrate reactants and products.
8. Regulatory mechanisms must be in place to control enzyme activity and metabolic flux.
9. Transport systems must exist to move substrates and products between compartments.
10. A system for maintaining genomic information encoding these enzymes must be present.

These requirements present several contradictions:
- The need for a complex, interdependent enzyme system conflicts with the assumption of simpler precursor systems.
- The requirement for specific regulatory mechanisms contradicts the presumed lack of sophisticated control systems in early cells.
- The need for compartmentalization conflicts with models proposing metabolism-first scenarios in open prebiotic environments.

4. Relevant Scientific Terminology

Metabolic pathways, enzyme catalysis, biosynthesis, metabolic flux, cofactors, coenzymes, ATP, cellular compartmentalization, metabolic regulation, transport proteins, genome, transcription, translation.

5. Illustrative Examples

Consider the biosynthesis of tryptophan, one of the most complex amino acids. This pathway requires five enzymes (TrpA-E) working in a coordinated sequence. Each enzyme catalyzes a specific reaction, and the product of one reaction becomes the substrate for the next. The pathway also requires several cofactors, including pyridoxal phosphate and NADPH. The complexity of this single amino acid's biosynthesis illustrates the challenges faced in evolving a complete set of biosynthetic pathways.

6. Critical Examination of Current Theories

Current theories of early cellular evolution often struggle to explain the origin of complex, integrated metabolic systems. Models proposing a gradual evolution of metabolic pathways face the challenge of explaining how intermediate stages could have been functional and provided a selective advantage. The high degree of interdependence among metabolic enzymes suggests that many components would need to have evolved simultaneously, which is difficult to explain through traditional evolutionary mechanisms.

The RNA World hypothesis, while addressing some aspects of early information storage and catalysis, does not adequately explain the transition to the complex protein-based metabolic systems observed in all modern cells. The catalytic limitations of ribozymes compared to protein enzymes create significant hurdles for this model in explaining the origin of efficient metabolic pathways.

7. Suggestion for Further Discussion

The immense complexity and interdependence of metabolic pathways, particularly in amino acid biosynthesis, present not just significant challenges but potentially insurmountable obstacles to naturalistic explanations for the origin of life. The sophistication of enzymatic metabolic biosynthesis pathways, when compared to prebiotic amino acid synthesis, reveals a chasm that current origin of life models struggle to bridge. At the heart of this issue lies a problem of irreducible circularity: proteins are required to synthesize amino acids, yet amino acids are necessary to produce the proteins that synthesize them. This circular dependency creates a logically irreconcilable conundrum for step-wise evolutionary scenarios. Consider the minimum of 112 enzymes required for the biosynthesis of the 20 standard proteinogenic amino acids. Each of these enzymes is a complex molecular machine, precisely folded and often requiring specific cofactors. The probability of such a system arising spontaneously, without the very amino acids it produces, stretches the bounds of plausibility. Furthermore, the intricate network of metabolic reactions, characterized by scale-free topology and hierarchical organization, suggests that the removal of even a few key components would lead to systemic collapse. This all-or-nothing characteristic severely undermines gradualistic explanations for the emergence of these pathways. Current hypotheses, such as the RNA World, fail to adequately address this fundamental issue. While RNA may serve catalytic functions, the catalytic efficiency of ribozymes pales in comparison to protein enzymes, particularly for the complex reactions involved in amino acid biosynthesis. The gulf between prebiotic chemistry and the sophisticated enzymatic systems observed in even the simplest modern cells appears unbridgeable through known natural processes. This presents a profound challenge to naturalistic origin of life scenarios.

Future discussions must grapple with this core issue of irreducible circularity. While exploring the role of inorganic catalysts or simple organic molecules in facilitating early metabolic reactions may yield insights, such approaches do not resolve the fundamental protein-amino acid interdependency. Computational models and artificial chemistry simulations, while valuable tools, operate under assumptions and constraints that may not reflect prebiotic reality. They risk overlooking the true magnitude of the problem by simplifying the immense complexity of real biochemical systems. The protein-amino acid biosynthesis conundrum represents a critical challenge to naturalistic explanations for the origin of life. The lack of a plausible prebiotic route to overcome this hurdle necessitates a fundamental reevaluation of current origin of life models. Future research must not only address the origin of individual components but also confront the seemingly irreducible nature of the integrated biosynthetic system as a whole. This may require entertaining alternative hypotheses that go beyond conventional naturalistic frameworks.

5. Conclusion

The formation of amino acids and functional peptides under prebiotic conditions faces numerous significant challenges that current origin of life models struggle to overcome. These hurdles can be categorized into several key areas:

1. Precursor availability: The scarcity of fixed nitrogen and carbon sources, reactivity issues with organosulfur compounds, and instability of ammonia pose significant obstacles to amino acid synthesis.
2. Peptide bond formation: Thermodynamic and kinetic barriers result in extremely low equilibrium concentrations of even short peptides under prebiotic conditions, challenging models relying on spontaneous polypeptide formation.
3. Quantity and concentration: Achieving the required millimolar concentrations of amino acids for primitive life far exceeds known prebiotic synthesis capabilities. The absence of eight "never-observed" proteinogenic amino acids in prebiotic experiments further complicates the picture.
4. Stability-reactivity paradox: Amino acids must remain stable enough to accumulate while being reactive enough to form peptides without enzymatic assistance, presenting a delicate balance difficult to achieve in prebiotic environments.

These challenges often involve mutually exclusive or contradictory requirements, making their simultaneous fulfillment under naturalistic scenarios highly improbable given our current understanding. The quantitative data and empirical findings presented in this review strongly suggest that the spontaneous emergence of a minimal functional proteome through purely naturalistic processes faces formidable obstacles.

To advance our understanding of life's origins, future research should:

1. Focus on specific mechanisms that could potentially overcome these challenges.
2. Encourage interdisciplinary approaches combining chemistry, biology, and geoscience.
3. Critically evaluate assumptions underlying current models in light of empirical data.
4. Explore alternative scenarios or environments that might provide the necessary conditions for amino acid and peptide formation.
5. Aim for incremental advances in understanding rather than comprehensive theories, given the complexity of the problem.

By addressing these points, the scientific community can better navigate the significant hurdles associated with the prebiotic formation of amino acids and peptides, potentially leading to more plausible models for the origin of life or revealing the need for alternative explanations.

References: 

2.1  Challenges in the Availability of Precursors for Prebiotic Amino Acid Synthesis

1. Nogal, N., Sanz-Sánchez, M., Vela-Gallego, S., Ruiz-Mirazo, K., & de la Escosura, A. (2023). The protometabolic nature of prebiotic chemistry. Chemical Society Reviews, 52(17), 7229-7248. Link. (This review explores the concept of protometabolism in prebiotic chemistry and its implications for the origin of life.)

2. Tran, Q.P., Yi, R., & Fahrenbach, A.C. (2023). Towards a prebiotic chemoton – nucleotide precursor synthesis driven by the autocatalytic formose reaction. Chemical Science, 14(25), 6999-7008. Link. (This study investigates the synthesis of nucleotide precursors using the formose reaction in a prebiotic context.)

3. Peters, S., Semenov, D., Hochleitner, R., & Trapp, O.E. (2023). Synthesis of prebiotic organics from CO2 by catalysis with meteoritic and volcanic particles. Scientific Reports, 13(1), 7054. Link. (This research examines the synthesis of organic compounds from CO2 using meteoritic and volcanic particles as catalysts under prebiotic conditions.)

Further references: 
Stuart, A.H., Rammu, H., & Lane, N. (2023). Prebiotic Synthesis of Aspartate Using Life's Metabolism as a Guide. Reproductive and developmental Biology, 13(5), 1177. Link. (This study investigates the prebiotic synthesis of aspartate using metabolic pathways found in modern life as a guide.)

Magrino, T., Pietrucci, F., & Saitta, A.M. (2021). Step by Step Strecker Amino Acid Synthesis from Ab Initio Prebiotic Chemistry. Journal of Physical Chemistry Letters, 12(9), 2376-2382. Link. (This work uses ab initio simulations to model a step-by-step Strecker synthesis of amino acids under prebiotic conditions.)

Ashe, K. (2018). Studies towards the prebiotic synthesis of nucleotides and amino acids. Doctoral thesis, University of Cambridge. Link. (This thesis explores various routes for the prebiotic synthesis of both nucleotides and amino acids.)

McDonald, G.D., & Storrie-Lombardi, M.C. (2010). Biochemical constraints in a protobiotic earth devoid of basic amino acids: the "BAA(-) world". Astrobiology, 10(10), 989-1000. Link. (This paper proposes a "BAA(-) world" hypothesis, exploring biochemical constraints in a protobiotic Earth lacking basic amino acids.)

Engel, M.H., & Perry, R.S. (2008). The origins of amino acids in ancient terrestrial and extraterrestrial materials. Proceedings of SPIE, 7097, 70970O. Link. (This review examines evidence for amino acid origins in ancient terrestrial and extraterrestrial materials.)

2.2 Challenges of Prebiotic Peptide Bond Formation

4. Nogal, N., Sanz-Sánchez, M., Vela-Gallego, S., Ruiz-Mirazo, K., & de la Escosura, A. (2023). The protometabolic nature of prebiotic chemistry. Chemical Society Reviews, 52(17), 7229-7248. Link. (This review explores the concept of protometabolism in prebiotic chemistry and its implications for the origin of life.)

5. Diederich, P., Geisberger, T., Yan, Y., Seitz, C., Ruf, A., Huber, C., Hertkorn, N., & Schmitt-Kopplin, P. (2023). Formation, stabilization and fate of acetaldehyde and higher aldehydes in an autonomously changing prebiotic system emerging from acetylene. Communications Chemistry, 6(1), 69. Link. (This study investigates the formation and behavior of aldehydes in a prebiotic system derived from acetylene.)

6. Zhang, W. (2023). The formation and stability of homochiral peptides in aqueous prebiological environment in the Earth's crust. arXiv preprint. Link. (This preprint examines the formation and stability of homochiral peptides in prebiotic aqueous environments within the Earth's crust.)

7. Chi, Y., Li, X.Y., Chen, Y., Zhang, Y., Liu, Y., Gao, X., & Zhao, Y. (2022). Prebiotic formation of catalytically active dipeptides via trimetaphosphate activation. Chemistry - An Asian Journal, 17(23), e202200926. Link. (This research demonstrates the prebiotic formation of catalytically active dipeptides using trimetaphosphate activation.)

Further references: 

Szilagyi, R.K. (2023). Peptide condensation and hydrolysis mechanisms from a proton-transfer network perspective. Organic and Biomolecular Chemistry, 21(21), 3974-3987. Link. (This study explores peptide formation and breakdown mechanisms from a proton-transfer perspective.)

Sydow, C., Sauer, F., Siegle, A.F., & Trapp, O. (2022). Iron‐mediated peptide formation in water and liquid sulfur dioxide under prebiotically plausible conditions. ChemSystemsChem, 4(5), e202200034. Link. (This work investigates iron-mediated peptide formation under prebiotic conditions.)
El Samrout, O., Berlier, G., Lambert, J.F., & Martra, G. (2023). Polypeptide Chain Growth Mechanisms and Secondary Structure Formation in Glycine Gas-Phase Deposition on Silica Surfaces. Journal of Physical Chemistry B, 127(13), 3017-3028. Link. (This study examines polypeptide formation on silica surfaces through gas-phase deposition.)

Trapp, O., Sauer, F., Haas, M., Sydow, C., Siegle, A.F., & Lauer, C. (2021). Peptide formation as on the early Earth: from amino acid mixtures to peptides in sulphur dioxide. Research Square. Link. (This preprint explores peptide formation in sulfur dioxide as a model for early Earth conditions.)

Stolar, T., Grubešić, S., Cindro, N., Meštrović, E., Užarević, K., & Hernández, J.G. (2021). Mechanochemical Prebiotic Peptide Bond Formation. Angewandte Chemie, 133(22), 12678-12682. Link. (This paper investigates mechanochemical methods for prebiotic peptide bond formation.)

Comte, D., Lavy, L., Bertier, P., Calvo, F., Daniel, I., Farizon, B., Farizon, M., & Märk, T.D. (2023). Glycine Peptide Chain Formation in the Gas Phase via Unimolecular Reactions. Journal of Physical Chemistry A, 127(8 ), 1768-1776. Link. (This study examines glycine peptide chain formation through gas-phase unimolecular reactions.)

Rousseau, P., Piekarski, D.G., Capron, M., Domaracka, A., Adoui, L., Martín, F., Alcamí, M., Díaz-Tendero, S., & Huber, B.A. (2020). Polypeptide formation in clusters of β-alanine amino acids by single ion impact. Nature Communications, 11(1), 3818. Link. (This work demonstrates polypeptide formation in β-alanine clusters through single ion impact.)

2.3  Quantity and Concentration: Challenges in Prebiotic Amino Acid Availability

8.Rolf, J., Handke, J., Burzinski, F., Luetz, S., & Rosenthal, K. (2023). Amino acid balancing for the prediction and evaluation of protein concentrations in cell-free protein synthesis systems. Biotechnology Progress, 39(5), e3373. Link. (This study investigates amino acid balancing for optimizing protein synthesis in cell-free systems.)

9. (2023). Amino acid balancing for the prediction and evaluation of protein concentrations in cell-free protein synthesis systems. arXiv preprint. Link. (This preprint discusses amino acid balancing techniques for cell-free protein synthesis systems.)

10. (2023). Geochemical and Photochemical Constraints on S[IV] Concentrations in Natural Waters on Prebiotic Earth. ESSOAr. Link. (This study examines the constraints on sulfur concentrations in prebiotic Earth's natural waters.)

11. Gómez Ortega, J., Raubenheimer, D., Tyagi, S., Mirth, C.K., & Piper, M.D.W. (2023). Biosynthetic constraints on amino acid synthesis at the base of the food chain may determine their use in higher-order consumer genomes. PLOS Genetics, 19(5), e1010635. Link. (This research explores how biosynthetic constraints on amino acids at lower trophic levels may influence their use in higher-order organisms' genomes.)

2.4  Stability and Reactivity: The Prebiotic Amino Acid Paradox

12. Stuart, A.H., Rammu, H., & Lane, N. (2023). Prebiotic Synthesis of Aspartate Using Life's Metabolism as a Guide. Reproductive and developmental Biology, 13(5), 1177. Link. (This study investigates the prebiotic synthesis of aspartate using metabolic pathways found in modern life as a guide.)

13. Holden, D.T., Morato, N.M., & Cooks, R.G. (2022). Aqueous microdroplets enable abiotic synthesis and chain extension of unique peptide isomers from free amino acids. Proceedings of the National Academy of Sciences of the United States of America, 119(44), e2212642119. Link. (This research demonstrates the abiotic synthesis and chain extension of peptide isomers in aqueous microdroplets, providing insights into potential prebiotic peptide formation mechanisms.)

2.5 Thermodynamic and Kinetic Barriers to Polymerization

14. Vaida, V., & Deal, A.M. (2022). Peptide synthesis in aqueous microdroplets. Proceedings of the National Academy of Sciences of the United States of America, 119(50), e2216015119. Link. (This study investigates the synthesis of peptides in aqueous microdroplets, providing insights into potential prebiotic chemistry mechanisms.)

15. Carvalho-Silva, V.H., Coutinho, N.D., & Aquilanti, V. (2020). From the Kinetic Theory of Gases to the Kinetics of Rate Processes: On the Verge of the Thermodynamic and Kinetic Limits. Molecules, 25(9), 2098. Link. (This review explores the connections between kinetic theory of gases and the kinetics of rate processes, discussing thermodynamic and kinetic limits relevant to chemical reactions.)

Further references:
Royal Truman and Charles McCombs, Negligible concentrations of peptides form in water: part 1 - using high temperatures or high pH​​J. Creation 38(1):126135, 2024.
Royal Truman, Change Tan, and Charles McCombs, Insignificant concentrations of peptides form in water: part 2-using moderate temperaturesJ. Creation 38(1):136‒149, 2024.
Chemical evolution of amino acids and proteins? Impossible!!
https://reasonandscience.catsboard.com/t2887-chemical-evolution-of-amino-acids-and-proteins-impossible

3.1 Thermodynamic and Kinetic Barriers to Prebiotic Polypeptide Formation

16. Harold, S.E., Warf, S.L., & Shields, G.C. (2023). Prebiotic dimer and trimer peptide formation in gas-phase atmospheric nanoclusters of water. Physical Chemistry Chemical Physics, 25(31), 20890-20901. Link. (This study investigates the formation of small peptides in atmospheric water nanoclusters, providing insights into potential prebiotic chemistry mechanisms.)

17. Zhao, Q., Garimella, S.S., & Savoie, B.M. (2023). Thermally Accessible Prebiotic Pathways for Forming Ribonucleic Acid and Protein Precursors from Aqueous Hydrogen Cyanide. Journal of the American Chemical Society, 145(10), 5735-5745. Link. (This research explores thermally accessible pathways for the formation of RNA and protein precursors from hydrogen cyanide in aqueous environments.)

18. El Samrout, O., Berlier, G., Lambert, J.F., & Martra, G. (2023). Polypeptide Chain Growth Mechanisms and Secondary Structure Formation in Glycine Gas-Phase Deposition on Silica Surfaces. Journal of Physical Chemistry B, 127(13), 3017-3028. Link. (This study examines polypeptide formation on silica surfaces through gas-phase deposition of glycine.)

19. Comte, D., Lavy, L., Bertier, P., Calvo, F., Daniel, I., Farizon, B., Farizon, M., & Märk, T.D. (2023). Glycine Peptide Chain Formation in the Gas Phase via Unimolecular Reactions. Journal of Physical Chemistry A, 127 ( 8 ) , 1768-1776. Link. (This study examines glycine peptide chain formation through gas-phase unimolecular reactions.)

20. Chi, Y., Li, X.Y., Chen, Y., Zhang, Y., Liu, Y., Gao, X., & Zhao, Y. (2022). Prebiotic formation of catalytically active dipeptides via trimetaphosphate activation. Chemistry - An Asian Journal, 17(23), e202200926. Link. (This research demonstrates the prebiotic formation of catalytically active dipeptides using trimetaphosphate activation.)

3.2 Chirality Issues

20. van Dongen, S., Ahlal, I., Leeman, M., Kaptein, B., Kellogg, R.G., Baglai, I., & Noorduin, W.L. (2022). Chiral Amplification through the Interplay of Racemizing Conditions and Asymmetric Crystal Growth. Journal of the American Chemical Society, 144(49), 22344-22349. Link. (This study explores chiral amplification mechanisms involving racemization and asymmetric crystal growth.)

21. (2023). Origin of Biological Homochirality by Crystallization of an RNA Precursor on a Magnetic Surface. arXiv preprint. Link. (This preprint proposes a mechanism for the origin of biological homochirality through crystallization of RNA precursors on magnetic surfaces.)

22. Huber, L., & Trapp, O.E. (2022). Symmetry Breaking by Consecutive Amplification: Efficient Paths to Homochirality. Origins of Life and Evolution of Biospheres, 52(3), 227-241. Link. (This paper discusses symmetry breaking mechanisms leading to homochirality through consecutive amplification processes.)

23. (2021). Chapter 1. Asymmetric Autocatalysis: The Soai Reaction, an Overview. In Asymmetric Autocatalysis: From Stochastic to Deterministic (pp. 1-18). Royal Society of Chemistry. Link. (This book chapter provides an overview of asymmetric autocatalysis, focusing on the Soai reaction as a key example.)

3.3 Sequence and Structure Formation in Prebiotic Protein Evolution: A Critical Analysis

24. Scolaro, G., & Braun, E.L. (2023). The Structure of Evolutionary Model Space for Proteins across the Tree of Life. Biology, 12(2), 282. Link. (This study explores the evolutionary model space for proteins across diverse life forms, providing insights into protein evolution patterns.)

25. Bricout, R., Weil, D., Stroebel, D., Genovesio, A., & Roest Crollius, H. (2023). Evolution is not Uniform Along Coding Sequences. Molecular Biology and Evolution, 40(3), msad042. Link. (This research demonstrates that evolutionary rates vary along coding sequences, challenging the assumption of uniform evolution.)

26. Tretyachenko, V., Vymětal, J., Neuwirthová, T., Vondrášek, J., Fujishima, K., & Hlouchová, K. (2022). Modern and prebiotic amino acids support distinct structural profiles in proteins. Open Biology, 12(4), 220040. Link. (This study compares the structural profiles of proteins composed of modern versus prebiotic amino acids, offering insights into early protein evolution.)

27. Lesk, A.M., & Konagurthu, A.S. (2022). Protein structure prediction improves the quality of amino‐acid sequence alignment. Proteins, 90(5), 1154-1161. Link. (This paper demonstrates how advances in protein structure prediction can enhance the accuracy of amino acid sequence alignments.)

Further references: 
Truman, R., Racemization of amino acids under natural conditions: part 1 – a challenge to abiogenesis, J. Creation 36(1):114–121, 2022.
Truman, R., Racemization of amino acids under natural conditions: part 2 - kinetic and thermodynamic dataJ. Creation 36(2):7280, 2022.
Truman, R., Racemization of amino acids under natural conditions part 3 - condensation to form oligopeptidesJ. Creation 36(2) 8189, 2022.
Truman, R. and Schmidtgall, B., Racemization of amino acids under natural conditions: part 4 — racemization always exceeds the rate of peptide elongation in aqueous solution J. Creation 36(3):7481, 2022.
Truman, R., Racemization of amino acids under natural conditions: part 5 — exaggerated old age datesJ. Creation 37(1):6474, 2023.

3.4  Scale and Reproduction in Prebiotic Systems: A Critical Analysis

Mizuuchi, R., & Ichihashi, N. (2023). Minimal RNA self-reproduction discovered from a random pool of oligomers. Chemical Science, 14(22), 6246-6255. Link. (This study reports the discovery of minimal RNA self-reproduction from a random pool of oligomers, providing insights into potential prebiotic RNA replication mechanisms.)

Red'ko, V.G. (2020). Models of Prebiotic Evolution. Biology Bulletin Reviews, 11(1), 35-46. Link. (This review discusses various models of prebiotic evolution, examining theoretical approaches to understanding the origin of life.)

Belliveau, N.M., Chure, G., Hueschen, C.L., Garcia, H.G., Kondev, J., Fisher, D.S., Theriot, J.A., & Phillips, R. (2021). Fundamental limits on the rate of bacterial growth and their influence on proteomic composition. Cell Systems, 12(9), 924-944.e14. Link. (This research explores the fundamental limits on bacterial growth rates and how these constraints influence protein composition in cells.)

3.5 Amplification of Enantiomeric Excess

28. (2023). Amplification of Enantiomeric Excess without Any Chiral Source in Prebiotic Case. Preprints, 2023070287. Link. (This preprint discusses the amplification of enantiomeric excess in prebiotic conditions without an initial chiral source.)

29. Watanabe, N., Shoji, M., Miyagawa, K., Hori, Y., Boero, M., Umemura, M., & Shigeta, Y. (2023). Enantioselective amino acid interactions in solution. Physical Chemistry Chemical Physics, 25(20), 13741-13749. Link. (This study investigates enantioselective interactions between amino acids in solution.)

30. Sato, A., Shoji, M., Watanabe, N., Boero, M., Shigeta, Y., & Umemura, M. (2023). Origin of Homochirality in Amino Acids Induced by Lyman-α Irradiation in the Early Stage of the Milky Way. Astrobiology, 23(5), 587-596. Link. (This research explores the potential role of Lyman-α radiation in the early Milky Way in inducing homochirality in amino acids.)

31. Bocková, J., Jones, N.C., Topin, J., Hoffmann, S.V., & Meinert, C. (2023). Uncovering the chiral bias of meteoritic isovaline through asymmetric photochemistry. Nature Communications, 14(1), 3475. Link. (This study investigates the chiral bias of isovaline in meteorites through asymmetric photochemistry experiments.)

32. Shoji, M., Kitazawa, Y., Sato, A., Watanabe, N., Boero, M., Shigeta, Y., & Umemura, M. (2023). Enantiomeric Excesses of Aminonitrile Precursors Determine the Homochirality of Amino Acids. Journal of Physical Chemistry Letters, 14(8 ), 2094-2100. Link. (This paper demonstrates how enantiomeric excesses in aminonitrile precursors can lead to homochirality in amino acids.)

Further references: 
Truman, R., The origin of L-amino acid enantiomeric excess: part 1-by preferential photo- destruction using circularly polarized light? J. Creation 36(3):67-73, 2022.
Truman, R., Enantiomeric amplification of L amino acids part 1-irrelevant and discredited examplesJ. Creation 37(2):96104, 2023.
Truman, R., Enantiomeric amplification of L amino acids part 2—chirality induced by D-sugarsJ. Creation 37(2):105111, 2023.
Truman, R. and Basel, C., Enantiomeric amplification of L amino acids part 3—using chiral impuritiesJ. Creation 37(2):120111, 2023.
Truman, R., Enantiomeric amplification of L amino acids: part 4—based on subliming valineJ. Creation 37(3):79-83, 2023.
Truman, R. and Grocott, S., Enantiomeric amplification of L amino acids: part 5—sublimation based on serine octamersJ. Creation 37(3):84-89, 2023.
Truman, R., Enantiomeric amplification of L amino acids: part 6—sublimation using Asn, Thr, Asp, Glu, Ser mixturesJ. Creation 37(3):90-92, 2023.
Truman, R., Enantiomeric amplification of L-amino acids: part 7-using aspartic acid on an achiral Cu surfaceJ. Creation 38(1):51‒53, 2024.
Truman, R. and Basel, C., Enantiomeric amplification of L-amino acids: part 8-modification of eutectic point with special additivesJ. Creation 38(1):54‒59, 2024.             
Truman, R., Basel, C., and Grocott, S., Enantiomeric amplification of amino acids: part 9—enantiomeric separation via crystallizationJ. of Creation 38(2):62-67, 2024.
Truman, R., Basel, C., and Grocott, S., Enantiomeric amplification of amino acids: part 10—extraction of homochiral crystals accompanied by catalytic racemizationJ. of Creation 38(2):68-74, 2024.
Homochirality, an unresolved issue https://reasonandscience.catsboard.com/t1309-homochirality

4.1 Optimal Set of Amino Acids

33. Brown, S.M., Voráček, V., & Freeland, S.J. (2023). What Would an Alien Amino Acid Alphabet Look Like and Why?. Astrobiology, 23(5), 597-611. Link. (This study explores the potential characteristics of amino acid alphabets that might evolve in extraterrestrial life forms, considering various biochemical and evolutionary constraints.)

34. Caldararo, F. (2022). The genetic code is very close to a global optimum in a model of its origin taking into account both the partition energy of amino acids and their biosynthetic relationships. BioSystems, 218, 104613. Link. (This research proposes a model for the origin of the genetic code that considers both amino acid partition energy and biosynthetic relationships, suggesting the code is near a global optimum.)

4.2 Protein Folding and Chaperones

35. (2022). Friends in need: how chaperonins recognize and remodel proteins that require folding assistance. arXiv preprint. Link. (This preprint discusses the mechanisms by which chaperonin proteins recognize and assist in the folding of other proteins, providing insights into protein quality control systems.)



Last edited by Otangelo on Tue Jul 09, 2024 11:45 am; edited 3 times in total

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A Response to: Complexity is Not Enough: A Critical Analysis of the "Life by Design" Teleological Argument
https://www.academia.edu/115191829/Complexity_is_Not_Enough_A_Critical_Analysis_of_the_Life_by_Design_Teleological_Argument

Claim: The argument's first premise commits the fallacy of presenting a false trilemma, artificially narrowing the possibilities for abiogenesis down to only three options - natural law, chance, or design (Grasso, 2022). However, the origins of the life field propose numerous additional models beyond this simplistic triad. Modern research has uncovered promising pathways for abiogenesis through chemical affinity and molecular self-organization. For example, clays and mineral surfaces may have concentrated biomolecules and facilitated polymerization reactions (Miller, 2003).

Response: The argument that the trilemma of natural law, chance, or design for explaining abiogenesis is a false or overly simplistic categorization is mistaken. In fact, this trilemma provides a comprehensive framework that encompasses all possible explanations for the origin of life, including processes like chemical affinity and molecular self-organization. Chemical processes, while governed by natural laws, can lead to outcomes that are essentially random and unguided. This dual nature means that chemical affinity and molecular self-organization actually span both the "natural law" and "chance" categories in the trilemma:

1. Natural law: Chemical reactions follow the laws of physics and chemistry. The properties of atoms and molecules that allow for chemical affinity and self-organization are determined by these natural laws.
2. Chance: The specific outcomes of these chemical processes, particularly in complex systems like those involved in abiogenesis, are often unpredictable and can be considered random. The exact molecules that form, their concentrations, and their interactions are subject to chance events.

In the context of abiogenesis, this means that while natural laws provide the framework for chemical reactions to occur, the specific path to life and the exact molecules that ended up forming the first self-replicating systems would have been largely determined by chance events if design is excluded. This understanding actually strengthens the validity of the trilemma rather than undermining it. The trilemma doesn't require that each possibility be mutually exclusive. Instead, it acknowledges that the origin of life could involve interplay between natural law and chance, while still leaving room for the possibility of design. Therefore, chemical affinity and molecular self-organization are indeed covered by the trilemma, falling into both the "natural law" and "chance" categories. This dual categorization more accurately reflects the nature of chemical processes in the context of abiogenesis. The trilemma thus provides a robust and inclusive framework for discussing the origin of life, allowing for the consideration of both known and yet-to-be-discovered natural processes that could have led to abiogenesis, while also accounting for the role of chance and not excluding the possibility of design.

Claim: Lipid vesicles that self-assemble based on chemistry alone provide micro-environments potentially conducive to proto-life (Deamer, 2017). 

Response: Steven A. Benner (2014): The Asphalt Paradox: Lipids that provide tidy compartments under the close supervision of a graduate student (supporting a protocell first model for origins) are quite non-robust with respect to small environmental perturbations, such as a change in the salt concentration, the introduction of organic solvents, or a change in temperature.

Steven A. Benner's "Asphalt Paradox" highlights a significant challenge in the protocell-first model of abiogenesis, illuminating the complexities involved in the emergence of cellular life. This concept, introduced in 2014, points out a fundamental issue with the idea that the first step towards life was the formation of simple cell-like structures composed of lipid membranes encapsulating primitive genetic material. The paradox arises from the conflicting requirements for a protocell membrane. On one hand, it needs to be stable enough to maintain its structure and protect its contents. On the other hand, it must be dynamic enough to allow for the exchange of materials necessary for metabolism and replication. This delicate balance is at the heart of the Asphalt Paradox. Benner's observation emphasizes that while lipid vesicles can be created and maintained under controlled laboratory conditions, they are far less stable in the variable conditions that would have existed on early Earth. These lipid structures are highly sensitive to environmental changes. Salt concentration fluctuations can disrupt the membrane integrity, organic solvents can dissolve or alter the lipid structure, and temperature changes can cause membranes to become too rigid or too fluid. This sensitivity raises questions about the prebiotic plausibility of such structures, as the conditions required to form and maintain these delicate protocells may not have been readily available or sustainable in early Earth environments. Furthermore, maintaining the integrity of these protocells against environmental perturbations would require a constant input of energy, which may not have been available in primitive conditions. This energy requirement adds another layer of complexity to the already challenging scenario of early life formation. The Asphalt Paradox has led researchers to consider alternative models for the origin of life, such as the "metabolism-first" hypothesis or models involving more robust compartments like mineral pores. It also raises questions about how such sensitive structures could have evolved into the more robust cell membranes we see in modern organisms.

Claim: Experiments demonstrate amino acids forming peptides, nucleotides forming RNA chains, and lipids forming vesicles naturally when conditions allow (Sutherland, 2017).

Response:  The paper: The Hurdles to Getting Amino Acids and Functional Peptides for the First Life Prebiotically Link demonstrates the major challenges faced in the prebiotic formation of amino acids and functional proteins - a critical step in the origin of life. The author systematically outlines several key hurdles, including:

Scarcity of fixed nitrogen and carbon sources needed for amino acid synthesis
Difficulty in obtaining reactive sulfur compounds required for certain amino acids
Rapid photochemical decomposition of ammonia, a crucial nitrogen source
Thermodynamic and kinetic barriers to forming even short peptides prebiotically

The review concludes that the naturalistic emergence of a minimal functional proteome faces significant obstacles that the current origin of life models struggle to overcome.



Last edited by Otangelo on Tue Jul 09, 2024 2:34 pm; edited 2 times in total

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Otangelo


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A Short Tale of the Origin of Proteins and Ribosome Evolution
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9694802/

Here's a summary of the main claims and points made in the paper:

1. The building blocks of life (amino acids and nucleotides) were likely present in early Earth conditions and could have formed spontaneously in a prebiotic soup.
2. Peptides and RNA likely coevolved in the early stages of life, with the ribosome being a key product of this coevolution.
3. The RNA world hypothesis suggests that RNA was a central molecule in early life, capable of storing information and catalyzing reactions.
4. Peptides may have played a more central role in early life than previously thought, with the ability to form easily in prebiotic conditions.
5. The first peptides likely arose through condensation and wet-dry cycles, possibly assembling into higher-order structures similar to amyloid formation.
6. Intrinsically disordered proteins (IDPs) may represent an important step in the evolution of modern proteins due to their simplicity and plasticity.
7. The ribosome's evolution is central to understanding the transition from chemical to Darwinian evolution, with the peptidyl transferase center (PTC) being one of the oldest parts.
8. The ribosome evolved through a series of phases, gradually acquiring complexity and function.
9. Ribosomal proteins coevolved with ribosomal RNA, with older protein regions interacting with more ancient RNA parts.
10. The study of ribosome structure and evolution has provided insights into the three domains of life (Archaea, Bacteria, and Eukarya) and the last universal common ancestor (LUCA).
11. The paper suggests a timeline for the evolution of life on Earth, from the formation of the planet to the great oxidation event and the adaptations that followed.

This review aims to provide general life scientists with an overview of how proteins could have arisen and how they are regulated in modern cells, focusing on the evolution of peptides, proteins, and ribosomes.

Refutation of Claims on the Origin of Proteins and Ribosome Evolution

1. Spontaneous Formation of Life's Building Blocks
Claim: Amino acids and nucleotides likely formed spontaneously in early Earth's prebiotic soup.
Refutation: Significant challenges exist for amino acid formation under prebiotic conditions. Specific atmospheric and environmental conditions may not have been prevalent. Stability and concentration of these amino acids are questionable due to rapid degradation and dilution.

2. Coevolution of Peptides and RNA
Claim: Peptides and RNA likely coevolved, with the ribosome as a key product.
Refutation: This scenario is highly speculative. RNA synthesis faces significant hurdles, including ribose formation difficulties and RNA instability in harsh prebiotic conditions. The simultaneous, interdependent evolution of peptides and RNA adds complexity, making this less plausible without concrete evidence.

3. RNA World Hypothesis
Claim: RNA was central in early life, capable of storing information and catalyzing reactions.
Refutation: Challenges include difficulty in forming ribonucleotides prebiotically and lack of a plausible prebiotic RNA replication pathway. These issues question RNA's feasibility as the initial life molecule.

4. Central Role of Peptides in Early Life
Claim: Peptides may have played a more central role in early life, forming easily in prebiotic conditions.
Refutation: Peptide bond formation faces significant barriers, including the need for specific catalysts and energy for condensation reactions. This suggests spontaneous formation of functional peptides is far from straightforward.

5. First Peptides and Higher-Order Structures
Claim: First peptides arose through condensation and wet-dry cycles, possibly forming amyloid-like structures.
Refutation: While wet-dry cycles can promote polymerization, resulting peptides would be random and unlikely to fold functionally. Higher-order structures require specific sequences, improbable in random assembly.

6. Intrinsically Disordered Proteins (IDPs)
Claim: IDPs may represent an important step in protein evolution due to simplicity and plasticity.
Refutation: IDPs still require sequence specificity to function. Random generation of such sequences is highly unlikely prebiotically. The transition to structured proteins involves significant unexplained evolutionary steps.

7. Ribosome Evolution and Chemical to Darwinian Transition
Claim: Ribosome evolution is key to understanding the transition from chemical to Darwinian evolution.
Refutation: The ribosome's complexity makes prebiotic assembly highly improbable. Formation of such a sophisticated nanomachine without a pre-existing, highly organized system seems unlikely.

8. Gradual Ribosome Evolution
Claim: The ribosome evolved through phases, gradually acquiring complexity and function.
Refutation: This assumes functional intermediate stages, which are highly speculative and lack experimental support.

9. Coevolution of Ribosomal Proteins and RNA
Claim: Ribosomal proteins coevolved with ribosomal RNA.
Refutation: This assumes a level of interdependence difficult to achieve prebiotically. Coordinated evolution without guiding selective pressure is questionable.

10. Ribosome Structure and Life Domains
Claim: Ribosome studies provide insights into life domains and LUCA.
Refutation: While providing evolutionary relationship insights, these do not confirm prebiotic feasibility of ribosome formation and function.

11. Timeline for Life's Evolution
Claim: A timeline is proposed from Earth's formation to the great oxidation event.
Refutation: The timeline might be oversimplified, ignoring myriad challenges in each evolutionary step. It appears more speculative than evidential.

These refutations highlight significant challenges in the proposed scenarios for protein origin and ribosome evolution, questioning their plausibility without further evidence.

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