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Monoamine transporter structure, function, dynamics, and drug discovery: a computational perspective.

ABSTRACT: With the breakthrough crystallization of the bacterial leucine transporter protein LeuT, the first available X-ray structure for the neurotransmitter/sodium symporter family, development of 3-D computational models is suddenly essential for structure-function studies on the plasmalemmal monoamine transporters (MATs). LeuT-based MAT models have been used to guide elucidation of substrate and inhibitor binding pockets, and molecular dynamics simulations using these models are providing insight into conformations involved in the substrate translocation cycle. With credible MAT models finally in hand, structure-based virtual screening for novel ligands is yielding lead compounds toward the development of new medications for psychostimulant dependence, attention deficit hyperactivity, depression, anxiety, schizophrenia, and other disorders associated with dopamine, norepinephrine, or serotonin dysregulation.

SUBMITTER: Manepalli S

PROVIDER: S-EPMC3475841 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Monoamine transporter structure, function, dynamics, and drug discovery: a computational perspective.

Manepalli Sankar S Surratt Christopher K CK Madura Jeffry D JD Nolan Tammy L TL

The AAPS journal 20120824 4

With the breakthrough crystallization of the bacterial leucine transporter protein LeuT, the first available X-ray structure for the neurotransmitter/sodium symporter family, development of 3-D computational models is suddenly essential for structure-function studies on the plasmalemmal monoamine transporters (MATs). LeuT-based MAT models have been used to guide elucidation of substrate and inhibitor binding pockets, and molecular dynamics simulations using these models are providing insight int ...[more]

PMID: 22918625

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