title: Molecular dynamics simulation of d-Benzedrine transmitting through molecular channels within D3R.
abstract: Dex-Benzedrine (known as d-Benzedrine or SAT) acts in dopamine receptors of central nerve cell system. In clinic, SAT is used to treat a variety of diseases; meanwhile, it has dependence and addiction. In order to investigate the pharmacology and addiction mechanisms of SAT as a medicine, in this paper, we have studied the structure of D3R complex protein with SAT, and based on which, using potential mean force with umbrella samplings and the simulated phospholipid bilayer membrane (or POPC bilayer membrane), the molecular dynamics simulation was performed to obtain free energy changes upon the trajectories for SAT moving along the molecular channels within D3R. The free energy change for SAT transmitting toward the outside of cell along the functional molecular channel within D3R is 83.5 kJ mol-1. The change of free energy for SAT to permeate into the POPC bilayer membrane along the protective molecular channel within D3R is 87.7 kJ mol-1. Our previous work gave that the free energy for Levo-Benzedrine (RAT) transmitting toward the outside of cell along the functional molecular channel within D3R is 91.4 kJ mol-1, while it is 117.7 kJ mol-1for RAT to permeate into the POPC bilayer membrane along the protective molecular channel within D3R. The values of free energy suggest that SAT relatively prefers likely to pass through the functional molecular channel within D3R for increasing the release of dopamine molecules resulting in a variety of functional effects for SAT. The obtained results show that the pharmacology and addiction mechanisms of SAT as a drug are closely related to the molecular dynamics and mechanism for SAT transmitting along molecular channels within D3R.
authors.affiliation: a Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology and Pharmacy Academy , Yunnan University , Kunming 650091 , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: a Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology and Pharmacy Academy , Yunnan University , Kunming 650091 , China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: a Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology and Pharmacy Academy , Yunnan University , Kunming 650091 , China.
authors.forename: Aijing
authors.initials: A
authors.lastname: Li
authors.affiliation: a Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology and Pharmacy Academy , Yunnan University , Kunming 650091 , China.
authors.forename: Si-Chuan
authors.initials: SC
authors.lastname: Xu
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009038:Motion; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D050637:Receptors, Dopamine D3 / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D050637:Receptors, Dopamine D3; C000625945:benzedrine; D004298:Dopamine
keywords: D3R; MD simulation; POPC; SAT; free energy