DPP-4与氰基吡咯烷类抑制剂相互作用的分子动力学模拟

Molecular dynamics simulation of binding of cyanopyrrolidine inhibitors to dipeptidyl peptidase-4( DPP-4)

通过分子对接、分子动力学(MD)模拟和自由能分析的方法研究3种氰基吡咯烷抑制剂与二肽基肽酶-4(DPP-4)之间的成键机制,分析和讨论3种抑制剂与二肽基肽酶之间的静电相互作用、范德华相互作用。用MM-PBSA方法计算得到的3种抑制剂的结合自由能与实验测得的结果是一致的。抑制剂与残基所形成的氢键能够使抑制剂稳定在结合位点。由残基Tyr631和Tyr666与抑制剂形成的范德华相互作用对结合自由能起到关键作用,并且显著地将3种不同抑制剂的生物活性区分开来。

The binding nechanism between three cyanopyrrolidine inhibitors and DPP-4 was investigated by molecular docking,molecular dynamics （MD） simulation and binding free energy analysis.The electrostatic and van der Waals interactions of the three inhibitors with DPP-4 were analyzed and discussed.The computed binding free energies using MM-PBSA method were in qualitatively agreement with experimental inhibitory potency of three inhibitors.The hydrogen bonds of inhibitors could stabilize the inhibitors in binding sites.The van der Waals interactions,between the inhibitors and residue Tyr631 and Tyr666 showed the key contributions to the binding free energy and played an important role in distinguishing the variant bioactivity of three inhibitors.