A molecular dynamics study on opioid activities of biphalin molecule |
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Authors: | Jin-Yuan Hsieh Tzen-Yuh Chiang Jun-Liang Chen Yun-Wen Chen Hong-Chang Lin Chi-Chuan Hwang |
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Institution: | (1) Department of Mechanical Engineering, Ming Hsin University of Science and Technology, Hsinchu, 30401, Taiwan;(2) Institute of Precision Mechatronic Engineering, Ming Hsin University of Science and Technology, Hsinchu, 30401, Taiwan;(3) Department of Life Sciences, National Cheng Kung University, Tainan, 701, Taiwan;(4) Department of Mechanical Engineering, Wu Feng Institute of Technology, Minsyong, Chiayi, 62153, Taiwan;(5) Department of Engineering Science, National Cheng Kung University, Tainan, 701, Taiwan; |
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Abstract: | 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-NH2 were performed to investigate the cause of the increased μ and δ 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 C4a - C4¢- N9 - N10 {\hbox{C}}_4^{\alpha } - {{\hbox{C}}_4}\prime - {{\hbox{N}}_9} - {{\hbox{N}}_{{10}}} and N9 - N10 - C5¢- C5a {{\hbox{N}}_9} - {{\hbox{N}}_{{10}}} - {{\hbox{C}}_5}\prime - {\hbox{C}}_5^{\alpha } , which in turn increase the opportunity of conformations for binding to μ or δ receptors. Meanwhile, the connection of the
two active tetrapeptide fragments of biphalin also results in the constrained side chain torsion angle χ2 at one of the two residues Phe. This constrained side chain torsion angle not only significantly increases the δ receptor
binding affinity but also makes most of the δ receptor binding conformations of biphalin bind to the δ receptor through the
fragment containing the mentioned residue Phe. |
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