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

07:00 EST 12th December 2017 | BioPortfolio

Summary of "A Quantitative Assessment of the Energetics of Dopamine Translocation by Human Dopamine Transporter."

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, simulations 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 (OFS) to the inward-facing state (IFS), on the other hand, require a dual-boost accelerated molecular dynamics (aMD) simulations. We present results on DA binding/unbinding energetics under different conditions, as well as the conformational energy landscape of hDAT in both DA-bound and -unbound states. The study provides a tractable method of approach for quantitative evaluation of substrate binding energetics and efficient estimation of conformational energy landscape, in general.

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This article was published in the following journal.

Name: The journal of physical chemistry. B
ISSN: 1520-5207
Pages:

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