CovET: A covariation-evolutionary trace method that identifies protein structure-function modules.

ABSTRACT: Measuring the relative effect that any two sequence positions have on each other may improve protein design or help better interpret coding variants. Current approaches use statistics and machine learning but rarely consider phylogenetic divergences which, as shown by Evolutionary Trace studies, provide insight into the functional impact of sequence perturbations. Here, we reframe covariation analyses in the Evolutionary Trace framework to measure the relative tolerance to perturbation of each residue pair during evolution. This approach (CovET) systematically accounts for phylogenetic divergences: at each divergence event, we penalize covariation patterns that belie evolutionary coupling. We find that while CovET approximates the performance of existing methods to predict individual struc

SUBMITTER: Konecki DM 

PROVIDER: S-EPMC10338321 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature