Allostery and Epistasis: Emergent Properties of Anisotropic Networks.

ABSTRACT: Understanding the underlying mechanisms behind protein allostery and non-additivity of substitution outcomes (i.e., epistasis) is critical when attempting to predict the functional impact of mutations, particularly at non-conserved sites. In an effort to model these two biological properties, we extend the framework of our metric to calculate dynamic coupling between residues, the Dynamic Coupling Index (DCI) to two new metrics: (i) EpiScore, which quantifies the difference between the residue fluctuation response of a functional site when two other positions are perturbed with random Brownian kicks simultaneously versus individually to capture the degree of cooperativity of these two other positions in modulating the dynamics of the functional site and (ii) DCIasym, which measures the deg

SUBMITTER: Campitelli P 

PROVIDER: S-EPMC7517209 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature