Structural Insights into Hearing Loss Genetics from Polarizable Protein Repacking.

ABSTRACT: Hearing loss is associated with ∼8100 mutations in 152 genes, and within the coding regions of these genes are over 60,000 missense variants. The majority of these variants are classified as "variants of uncertain significance" to reflect our inability to ascribe a phenotypic effect to the observed amino acid change. A promising source of pathogenicity information is biophysical simulation, although input protein structures often contain defects because of limitations in experimental data and/or only distant homology to a template. Here, we combine the polarizable atomic multipole optimized energetics for biomolecular applications force field, many-body optimization theory, and graphical processing unit acceleration to repack all deafness-associated proteins and thereby improve average str

SUBMITTER: Tollefson MR 

PROVIDER: S-EPMC6697528 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature