Localized structural frustration for evaluating the impact of sequence variants.

ABSTRACT: Population-scale sequencing is increasingly uncovering large numbers of rare single-nucleotide variants (SNVs) in coding regions of the genome. The rarity of these variants makes it challenging to evaluate their deleteriousness with conventional phenotype-genotype associations. Protein structures provide a way of addressing this challenge. Previous efforts have focused on globally quantifying the impact of SNVs on protein stability. However, local perturbations may severely impact protein functionality without strongly disrupting global stability (e.g. in relation to catalysis or allostery). Here, we describe a workflow in which localized frustration, quantifying unfavorable local interactions, is employed as a metric to investigate such effects. Using this workflow on the Protein Databank

SUBMITTER: Kumar S 

PROVIDER: S-EPMC5137452 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature