Proteome-Wide Structural Computations Provide Insights into Empirical Amino Acid Substitution Matrices.

ABSTRACT: The relative contribution of mutation and selection to the amino acid substitution rates observed in empirical matrices is unclear. Herein, we present a neutral continuous fitness-stability model, inspired by the Arrhenius law (qij=aije-ΔΔGij). The model postulates that the rate of amino acid substitution (i→j) is determined by the product of a pre-exponential factor, which is influenced by the genetic code structure, and an exponential term reflecting the relative fitness of the amino acid substitutions. To assess the validity of our model, we computed changes in stability of 14,094 proteins, for which 137,073,638 in silico mutants were analyzed. These site-specific data were summarized into a 20 square matrix, whose entries, ΔΔGij, were obtained after averaging through all the sites in a

SUBMITTER: Aledo P 

PROVIDER: S-EPMC9821064 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature