Thermodynamic Coupling Function Analysis of Allosteric Mechanisms in the Human Dopamine Transporter.

ABSTRACT: Allostery plays a crucial role in the mechanism of neurotransmitter-sodium symporters, such as the human dopamine transporter. To investigate the molecular mechanism that couples the transport-associated inward release of the Na⁺ ion from the Na2 site to intracellular gating, we applied a combination of the thermodynamic coupling function (TCF) formalism and Markov state model analysis to a 50-μs data set of molecular dynamics trajectories of the human dopamine transporter, in which multiple spontaneous Na⁺ release events were observed. Our TCF approach reveals a complex landscape of thermodynamic coupling between Na⁺ release and inward-opening, and identifies diverse, yet well-defined roles for different Na⁺-coordinating residues. In particular,

SUBMITTER: LeVine MV 

PROVIDER: S-EPMC5773750 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature