Acta Phys. -Chim. Sin. ›› 2016, Vol. 32 ›› Issue (4): 907-920.doi: 10.3866/PKU.WHXB201601141

• ARTICLE • Previous Articles     Next Articles

Molecular Dynamics Simulation for Levo-Benzedrine to Transmit through Molecular Channels within D3R

Wei XIE,Ze-Ren XU,Ming WANG,Si-Chuan XU*()   

  • Received:2015-11-04 Published:2016-04-07
  • Contact: Si-Chuan XU E-mail:sichuan@ynu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(21163024, 21563032)

Abstract:

Levo-benzedrine (also known as L-benzedrine or RAT) acts in dopamine receptors of the central nerve cell. In a clinical setting, RAT is used to treat a variety of diseases; however, it can also result in physical dependence and addiction. To investigate the pharmacology and addiction mechanism of RAT as a medication, we have obtained the optimized structure of the dopamine Ⅲ receptor (D3R) complex protein with RAT. On the basis of this structure, by using the method of potential mean force (PMF) with umbrella sampling and the simulated phospholipid bilayer membrane (also known as the POPC bilayer membrane), the molecular dynamics simulation was performed to obtain the trajectories with the changes of free energy on the structure for RAT to move along the molecular channels within D3R. The change of free energy for RAT to transfer toward the outside of the cell along the functioning molecular channel within D3R is 91.4 kJ·mol-1. The change of free energy for RAT to transfer into the POPC bilayer membrane along the protecting molecular channel within D3R is 117.7 kJ·mol-1. These results suggest that RAT is more likely to exert its molecular functions and to increase the release of functioning dopamine molecules by transferring along the functioning molecular channel within D3R, which result in a variety of functional effects by RAT including dependence and addiction. The obtained results show that the pharmacology and addiction mechanism of RAT as a medication are closely related to the molecular dynamics and mechanism for RAT to transfer along molecular channels within dopamine receptors.

Key words: L-Benzedrine, D3R, POPC, Molecular dynamics simulation, Free energy

MSC2000: 

  • O642