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.
Keywords: D3R; benzedrine; chirality; molecular dynamics simulation; molecular recognition.
© 2016 Wiley Periodicals, Inc.