Circuit topology predicts pathogenicity of missense mutations.

ABSTRACT: The contact topology of a protein determines important aspects of the folding process. The topological measure of contact order has been shown to be predictive of the rate of folding. Circuit topology is emerging as another fundamental descriptor of biomolecular structure, with predicted effects on the folding rate. We analyze the residue-based circuit topological environments of 21 K mutations labeled as pathogenic or benign. Multiple statistical lines of reasoning support the conclusion that the number of contacts in two specific circuit topological arrangements, namely inverse parallel and cross relations, with contacts involving the mutated residue have discriminatory value in determining the pathogenicity of human variants. We investigate how results vary with residue type and accordi

SUBMITTER: Woodard J 

PROVIDER: S-EPMC9543832 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature