Searching for a mechanistic description of pairwise epistasis in protein systems.

ABSTRACT: When two or more amino acid mutations occur in protein systems, they can interact in a nonadditive fashion termed epistasis. One way to quantify epistasis between mutation pairs in protein systems is by using free energy differences: ϵ = ΔΔG_1,2  - (ΔΔG₁  + ΔΔG₂ ) where ΔΔG refers to the change in the Gibbs free energy, subscripts 1 and 2 refer to single mutations in arbitrary order and 1,2 refers to the double mutant. In this study, we explore possible biophysical mechanisms that drive pairwise epistasis in both protein-protein binding affinity and protein folding stability. Using the largest available datasets containing experimental protein structures and free energy data, we derived statistical models for both binding and folding epistasis (ϵ) with simil

SUBMITTER: Barnes JE 

PROVIDER: S-EPMC9177791 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature