Disentangling contact and ensemble epistasis in a riboswitch.

ABSTRACT: Mutations introduced into macromolecules often exhibit epistasis, where the effect of one mutation alters the effect of another. Knowing the mechanisms that lead to epistasis is important for understanding how macromolecules work and evolve, as well as for effective macromolecular engineering. Here, we investigate the interplay between "contact epistasis" (epistasis arising from physical interactions between mutated residues) and "ensemble epistasis" (epistasis that occurs when a mutation redistributes the conformational ensemble of a macromolecule, thus changing the effect of the second mutation). We argue that the two mechanisms can be distinguished in allosteric macromolecules by measuring epistasis at differing allosteric effector concentrations. Contact epistasis manifests as nonaddit

SUBMITTER: Wonderlick DR 

PROVIDER: S-EPMC10183321 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature