Epistasis meets pleiotropy in shaping biophysical protein subspaces associated with antimicrobial resistance.

ABSTRACT: Protein space is a rich analogy for genotype-phenotype maps, where amino acid sequence is organized into a high-dimensional space that highlights the connectivity between protein variants. It is a useful abstraction for understanding the process of evolution, and for efforts to engineer proteins towards desirable phenotypes. Few framings of protein space consider how higher-level protein phenotypes can be described in terms of their biophysical dimensions, nor do they rigorously interrogate how forces like epistasis-describing the nonlinear interaction between mutations and their phenotypic consequences-manifest across these dimensions. In this study, we deconstruct a low-dimensional protein space of a bacterial enzyme (dihydrofolate reductase; DHFR) into "subspaces" corresponding to a set

SUBMITTER: Ogbunugafor CB 

PROVIDER: S-EPMC10104174 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature