1.12. Sequence and Structure Formation in Prebiotic Protein Emergence: 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].
1.12.1. 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.
1.12.2. 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
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].
1.12.1. 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.
1.12.2. 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
