About the Protein Space Vastness

TL;DR

This paper refines the estimate of the functional Protein Space size to about 10^9 proteins, providing insights into protein evolvability and mutation rates, which helps frame the vastness problem more realistically.

Contribution

It offers a simplified analysis that reduces the estimated functional Protein Space and provides a robust mutation rate estimate, improving understanding of protein evolvability.

Findings

Estimated functional Protein Space size ~10^9 proteins

Average mutation rate per amino acid ~1.23

Only a fraction of sequence space is accessible for functional evolution

Abstract

An accurate estimation of the Protein Space size, in light of the factors that govern it, is a long-standing problem and of paramount importance in evolutionary biology, since it determines the nature of protein evolvability. A simple analysis will enable us to, firstly, reduce an unrealistic Protein Space size of ~10^130 sequences, for a 100-residues polypeptide chain, to ~10^9 functional proteins and, secondly, estimate a robust average-mutation rate per amino acid (x ~1.23) and infer from it, in light of the protein marginal stability, that only a fraction of the sequence will be available at any one time for a functional protein to evolve. Although this result does not solve the Protein Space vastness problem, frames it in a more rational one.