title: Structural Basis and Mechanism of Chiral Benzedrine Molecules Interacting With Third Dopamine Receptor.
abstract: In order to investigate the chiral benzedrine molecules corresponding to their different characteristics in biochemical systems, we studied their interaction with D3 R using the docking method, molecular dynamic simulation, and quantum chemistry. The obtained results indicate that the active residues for R-benzedrine (RAT) bound with D3 R are Ala132, Asp133, and Tyr55, while Asn57, Asp133, Asp168, Cys172, Gly54, Trp24, and Vall136 act as the active residues for S-benzedrine (SAT). The different active pockets are observed for ART or SAT because they possess different active residues. The binding energies between RAT and SAT with D3 R were determined to be -44.0 kJ.mol(-1) and -71.2 kJ.mol(-1) , respectively. These results demonstrate that SAT within the studied pocket of D3 R has a stronger capability of binding with D3 R, while it is more feasible for RAT to leave from the interior positions of D3 R. In addition, the results suggest that the D3 R protein can recognize chiral benzedrine molecules and influence their different addictive and pharmacological effects in biochemical systems. Chirality 28:674-685, 2016. © 2016 Wiley Periodicals, Inc.
authors: Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology, Yunnan University, Kunming, China.
authors: Ming
authors: M
authors: Wang
authors: Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology, Yunnan University, Kunming, China.
authors: Wei
authors: W
authors: Xie
authors: Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology, Yunnan University, Kunming, China.
authors: Aijing
authors: A
authors: Li
authors: Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology, Yunnan University, Kunming, China. sichuan@ynu.edu.cn.
authors: Sichuan
authors: S
authors: Xu
mesh_terms: D020134:Catalytic Domain; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D050637:Receptors, Dopamine D3 / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D050637:Receptors, Dopamine D3; C000625945:benzedrine; D004298:Dopamine
keywords: D3R; benzedrine; chirality; molecular dynamics simulation; molecular recognition