Mechanism for cocaine blocking the transport of dopamine: insights from molecular modeling and dynamics simulations.

ABSTRACT: Molecular modeling and dynamics simulations have been performed to study how cocaine inhibits dopamine transporter (DAT) for the transport of dopamine. The computationally determined DAT-ligand binding mode is totally different from the previously proposed overlap binding mode in which cocaine- and dopamine-binding sites are the same (Beuming, T.; et al. Nat. Neurosci. 2008, 11, 780-789). The new cocaine-binding site does not overlap with, but is close to, the dopamine-binding site. Analysis of all results reveals that when cocaine binds to DAT, the initial binding site is likely the one modeled in this study because this binding site can naturally accommodate cocaine. Then cocaine may move to the dopamine-binding site after DAT makes some necessary conformational change and expands the bi

SUBMITTER: Huang X 

PROVIDER: S-EPMC2774931 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature