A molecular dynamics study on opioid activities of biphalin molecule

作者：Hsieh, Jin-Yuan; Chiang, Tzen-Yuh; Chen, Jun-Liang; Chen, Yun-Wen; Lin, Hong-Chang; Hwang, Chi-Chuan^*

来源：Journal of Molecular Modeling, 2011, 17(10): 2455-2464.

DOI：10.1007/s00894-010-0931-1

• Biphalin
• Molecular dynamics
• Opioid activities

Molecular dynamics simulations of the biphalin molecule, (Tyr-D-Ala-Gly-Phe-NH)(2), and the active tetrapeptide hydrazide, Tyr-D-Ala-Gly-Phe-NH-NH(2) were performed to investigate the cause of the increased mu and delta receptor binding affinities of the former over the latter. The simulation results demonstrate that the acylation of the two equal tetrapeptide fragments of biphalin produces the constrained hydrazide bridges C(4)(alpha) - C'(4) - N(9) - N(10) and N(9) - N(10) - C'(5) - C(5)(alpha), which in turn increase the opportunity of conformations for binding to mu or delta receptors. Meanwhile, the connection of the two active tetrapeptide fragments of biphalin also results in the constrained side chain torsion angle chi(2) at one of the two residues Phe. This constrained side chain torsion angle not only significantly increases the delta receptor binding affinity but also makes most of the delta receptor binding conformations of biphalin bind to the delta receptor through the fragment containing the mentioned residue Phe.

• 出版日期2011-10