Evolutionary Models of Amino Acid Substitutions Based on the Tertiary Structure of their Neighborhoods

BioRxiv : the Preprint Server for Biology
Elias PrimetisPavlos Pavlidis

Abstract

Intra-protein residual vicinities depend on the involved amino acids. Energetically favorable vicinities (or interactions) have been preserved, while unfavorable vicinities have been eliminated during evolution. We describe, statistically, the interactions between amino acids using resolved protein structures. Based on the frequency of amino acid interactions, we have devised an amino acid substitution model that implements the following idea: amino acids that have similar neighbors in the protein tertiary structure can replace each other, while substitution is more difficult between amino acids that prefer different spatial neighbors. Using known tertiary structures for α-helical membrane (HM) proteins, we build evolutionary substitution matrices. We constructed maximum likelihood phylogenies using our amino acid substitution matrices and compared them to widely-used methods. Our results suggest that amino acid substitutions are associated with the spatial neighborhoods of amino acid residuals.

Related Concepts

Biological Evolution
Membrane Proteins
Tertiary Protein Structure
Proximal
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Chemical Substitution
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