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ACS Chem Neurosci. 2016 Nov 16;7(11):1607-1613. Epub 2016 Sep 19.

Guidelines for Homology Modeling of Dopamine, Norepinephrine, and Serotonin Transporters.

Haddad Y1,2, Heger Z1,2, Adam V1,2.

Author information

1
Department of Chemistry and Biochemistry, Mendel University in Brno , Zemedelska 1, CZ-613 00 Brno, Czech Republic.
2
Central European Institute of Technology, Brno University of Technology , Purkynova 123, CZ-612 00 Brno, Czech Republic.

Abstract

The human dopamine, norepinephrine, and serotonin transporters (hDAT, hNET, and hSERT) are carriers of neurotransmitters and targets for many drugs. Pioneering works in the past three years to elucidate experimental models of the Drosophila dDAT and human hSERT structures will rapidly impact the field of neuroscience. Here, we evaluated automated homology-based human models of these transporters, employing systematic physics-based, knowledge-based, and empirical-based check. Modeling guidelines were conveyed with attention to the central binding site (S1), secondary binding site (S2), and the extracellular loops EL2 and EL4. Application of new experimental models (dDAT and hSERT) will improve the accuracy of homology models, previously utilizing prokaryotic leucine transporter (LeuT) structure, and provide better predictions of ligand interactions, which is required for understanding of cellular mechanisms and for development of novel therapeutics.

KEYWORDS:

Homology-based; dopamine transporter; norepinephrine transporter; protein structure; serotonin transporter; template-based

PMID:
27596073
DOI:
10.1021/acschemneuro.6b00242
[Indexed for MEDLINE]

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