Study On The Interaction Mechanism Between Amphetamine Chiral Molecules And Dopamine Third Receptor Membrane Proteins

Chirality,universally existing in nature,is an unusual characteristic.Benzedrine is a chiral molecule to have a pair of enantiomers represented by R-benzedrine(RAT)and S-benzedrine(SAT)respectively.Through investigating the chiral benzedrine molecules to interact with dopamine 3-subtype receptor(D3R protein),it will not only advance to understand its drug action and addiction with its other biologic functions,but also help to open out the molecular mechanism of membrane receptor protein recognizing and separating chiral molecules.In this thesis,at first,we used the docking technology to dock two kinds of chiral benzedrines into the interior positions of D3R protein for building the complex structures of D3R with chiral benzedrines;next,we used molecular dynamics simulations and Gromacs programs to simulate and optimize the built complex protein structure;and then,extracting every complexes of benzedrine with single residue from the optimized complex structures of D3R,we used quantum chemistry to calculate the interaction binding energies of every extracted complexes,on which to study and find the active residues for benzedrine binding within D3R structure and to locate the active pockets for RAT and SAT.The obtained results indicate that the residues for RAT binding within D3R structure are Ala132,Aspl33 and Tyr55,and those for SAT binding within D3R structure are Asn57,Asp133,Asp168,Cysl 72,Gly54,Trp24 and Vall136,from which observed are the different active residues and active pockets for ART and SAT.The binding energy between RAT and D3R protein is-44.1 kJ/mol,while it is-71.3 kJ/mol for SAT binding into D3R protein,from which their biding energies are also shown to be different,and SAT has a stronger capability binding into D3R protein and a longer time to stay within D3R protein,while for RAT it is more feasible to leave from the interior positions of D3R structure for exerting its biologic multifunction.The obtained experimental results further show that D3R protein reliably has the ability to recognize and distinguish chiral benzedrine molecules,and makes different chiral benzedrine molecules bring into playing various physiological functions,especially to make different chiral benzedrine molecules have different addictive ability and mechanisms as well as different pharmacological effects.