Protein-protein binding pathways and calculations of rate constants using fully-continuous, explicit-solvent simulations.

ABSTRACT: A grand challenge in the field of biophysics has been the complete characterization of protein-protein binding processes at atomic resolution. This characterization requires the direct simulation of binding pathways starting from the initial, unbound state and proceeding through states that are too transient to be captured by experiment. Here, we applied the weighted ensemble path sampling strategy to orchestrate atomistic simulation of protein-protein binding pathways. Our simulation generated 203 fully-continuous and independent pathways along with rate constants for the binding process involving the barnase and barstar proteins. Results reveal multiple binding pathways along a "funnel-like" free energy landscape in which the formation of the "encounter complex" intermediate is rate-limi

SUBMITTER: Saglam AS 

PROVIDER: S-EPMC6385678 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature