Identification of coevolving residues and coevolution potentials emphasizing structure, bond formation and catalytic coordination in protein evolution.

ABSTRACT: The structure and function of a protein is dependent on coordinated interactions between its residues. The selective pressures associated with a mutation at one site should therefore depend on the amino acid identity of interacting sites. Mutual information has previously been applied to multiple sequence alignments as a means of detecting coevolutionary interactions. Here, we introduce a refinement of the mutual information method that: 1) removes a significant, non-coevolutionary bias and 2) accounts for heteroscedasticity. Using a large, non-overlapping database of protein alignments, we demonstrate that predicted coevolving residue-pairs tend to lie in close physical proximity. We introduce coevolution potentials as a novel measure of the propensity for the 20 amino acids to pair among

SUBMITTER: Little DY 

PROVIDER: S-EPMC2651771 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature