Maximum-Likelihood Phylogenetic Inference with Selection on Protein Folding Stability.

ABSTRACT: Despite intense work, incorporating constraints on protein native structures into the mathematical models of molecular evolution remains difficult, because most models and programs assume that protein sites evolve independently, whereas protein stability is maintained by interactions between sites. Here, we address this problem by developing a new mean-field substitution model that generates independent site-specific amino acid distributions with constraints on the stability of the native state against both unfolding and misfolding. The model depends on a background distribution of amino acids and one selection parameter that we fix maximizing the likelihood of the observed protein sequence. The analytic solution of the model shows that the main determinant of the site-specific distributio

SUBMITTER: Arenas M 

PROVIDER: S-EPMC4833071 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature