Optimizing Stability in Dynamic Small-Molecule Binding Proteins.

ABSTRACT: The function of dynamic proteins is determined by the stability of distinct conformational states and the energy barriers that separate these states. For most dynamic proteins, the molecular details of the energy barriers are not known, implying a fundamental limit to the ability of protein design methods to engineer beneficial mutations without disrupting activity. We hypothesized that designing mutations that are compatible with structurally distinct equilibrium conformations may enable a reliable stability design. We focus on periplasmic binding proteins (PBPs), a superfamily of dynamic proteins that change conformation from open to closed states in response to binding their small-molecule ligands. We find that the evolutionary constrained space of allowed mutations computed for one con

SUBMITTER: Scherer M 

PROVIDER: S-EPMC12814167 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature