Selection pressures on evolution of ribonuclease H explored with rigorous free-energy-based design.

ABSTRACT: Understanding natural protein evolution and designing novel proteins are motivating interest in development of high-throughput methods to explore large sequence spaces. In this work, we demonstrate the application of multisite λ dynamics (MSλD), a rigorous free energy simulation method, and chemical denaturation experiments to quantify evolutionary selection pressure from sequence-stability relationships and to address questions of design. This study examines a mesophilic phylogenetic clade of ribonuclease H (RNase H), furthering its extensive characterization in earlier studies, focusing on E. coli RNase H (ecRNH) and a more stable consensus sequence (AncCcons) differing at 15 positions. The stabilities of 32,768 chimeras between these two sequences were computed using the MSλD fra

SUBMITTER: Hayes RL 

PROVIDER: S-EPMC10801872 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature