Multiscale Kinetic Modeling Reveals an Ensemble of Cl^-/H⁺ Exchange Pathways in ClC-ec1 Antiporter.

ABSTRACT: Despite several years of research, the ion exchange mechanisms in chloride/proton antiporters and many other coupled transporters are not yet understood at the molecular level. Here, we present a novel approach to kinetic modeling and apply it to ion exchange in ClC-ec1. Our multiscale kinetic model is developed by (1) calculating the state-to-state rate coefficients with reactive and polarizable molecular dynamics simulations, (2) optimizing these rates in a global kinetic network, and (3) predicting new electrophysiological results. The model shows that the robust Cl:H exchange ratio (2.2:1) can indeed arise from kinetic coupling without large protein conformational changes, indicating a possible facile evolutionary connection to chloride channels. The E148 amino acid residue is shown to

SUBMITTER: Mayes HB 

PROVIDER: S-EPMC5812667 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature