Mechanistic picture for conformational transition of a membrane transporter at atomic resolution.

ABSTRACT: During their transport cycle, ATP-binding cassette (ABC) transporters undergo large-scale conformational changes between inward- and outward-facing states. Using an approach based on designing system-specific reaction coordinates and using nonequilibrium work relations, we have performed extensive all-atom molecular dynamics simulations in the presence of explicit membrane/solvent to sample a large number of mechanistically distinct pathways for the conformational transition of MsbA, a bacterial ABC exporter whose structure has been solved in multiple functional states. The computational approach developed here is based on (i) extensive exploration of system-specific biasing protocols (e.g., using collective variables designed based on available low-resolution crystal structures) and (ii)

SUBMITTER: Moradi M 

PROVIDER: S-EPMC3839739 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature