ABCG2/BCRP transport mechanism revealed through kinetically excited targeted molecular dynamics simulations.

ABSTRACT: ABCG2/BCRP is an ABC transporter that plays an important role in tissue protection by exporting endogenous substrates and xenobiotics. ABCG2 is of major interest due to its involvement in multidrug resistance (MDR), and understanding its complex efflux mechanism is essential to preventing MDR and drug-drug interactions (DDI). ABCG2 export is characterized by two major conformational transitions between inward- and outward-facing states, the structures of which have been resolved. Yet, the entire transport cycle has not been characterized to date. Our study bridges the gap between the two extreme conformations by studying connecting pathways. We developed an innovative approach to enhance molecular dynamics simulations, 'kinetically excited targeted molecular dynamics', and successfully sim

SUBMITTER: Dudas B 

PROVIDER: S-EPMC9389183 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature