Coupled molecular dynamics mediate long- and short-range epistasis between mutations that affect stability and aggregation kinetics.

ABSTRACT: Multiple mutations are typically required to significantly improve protein stability or aggregation kinetics. However, when several substitutions are made in a single protein, the mutations can potentially interact in a nonadditive manner, resulting in epistatic effects, which can hamper protein-engineering strategies to improve thermostability or aggregation kinetics. Here, we have examined the role of protein dynamics in mediating epistasis between pairs of mutations. With Escherichia coli transketolase (TK) as a model, we explored the epistatic interactions between two single variants H192P and A282P, and also between the double-mutant H192P/A282P and two single variants, I365L or G506A. Epistasis was determined for several measures of protein stability, including the following:

SUBMITTER: Yu H 

PROVIDER: S-EPMC6255212 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature