Coevolving residues inform protein dynamics profiles and disease susceptibility of nSNVs.

ABSTRACT: The conformational dynamics of proteins is rarely used in methodologies used to predict the impact of genetic mutations due to the paucity of three-dimensional protein structures as compared to the vast number of available sequences. Until now a three-dimensional (3D) structure has been required to predict the conformational dynamics of a protein. We introduce an approach that estimates the conformational dynamics of a protein, without relying on structural information. This de novo approach utilizes coevolving residues identified from a multiple sequence alignment (MSA) using Potts models. These coevolving residues are used as contacts in a Gaussian network model (GNM) to obtain protein dynamics. B-factors calculated using sequence-based GNM (Seq-GNM) are in agreement with crystallographi

SUBMITTER: Butler BM 

PROVIDER: S-EPMC6289467 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature