Quantitative Assessment of the Energetics of Dopamine Translocation by Human Dopamine Transporter.

ABSTRACT: Computational evaluation of the energetics of substrate binding, transport, and release events of neurotransmitter transporters at the molecular level is a challenge, as the structural transitions of these membrane proteins involve coupled global and local changes that span time scales of several orders of magnitude, from nanoseconds to seconds. Here, we provide a quantitative assessment of the energetics of dopamine (DA) translocation through the human DA transporter (hDAT), using a combination of molecular modeling, simulation, and analysis tools. DA-binding and -unbinding events, which generally involve local configurational changes, are evaluated using free-energy perturbation or adaptive biasing force methods. The global transitions between the outward-facing state and the inward-faci

SUBMITTER: Cheng MH 

PROVIDER: S-EPMC5991911 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature