三氢-咪唑并[4,5-c]喹啉-4(5H)-酮衍生物与二肽基肽酶-4结合机理的理论研究

A Study on Binding Mechanism of 3H-imidazo[4,5-c]quinolin-4(5H)-ones to Dipeptidyl Peptidase Ⅳ Based on Molecular Dynamics Simulation

通过分子对接、分子动力学(MD)模拟和结合自由能分析的方法研究了三氢-咪唑并[4,5-c]喹啉-4(5H)-酮衍生物药物与二肽基肽酶之间的成键机制,分析和讨论了抑制剂和相邻残基之间的氢键和疏水相互作用.用MM-PBSA方法计算得到的4个抑制剂的结合自由能与实验上测得的结果是一致的.抑制剂与DPP-4的关键残基间的范德华相互作用对于体系的结合能有较大的贡献,并且是区分不同抑制剂生物活性的标志之一.

We apply molecular docking, molecular dynamics （MD）simulations and binding free energy analysis to investigate and reveal the binding mechanism between four 3H-imidazo [4,5-c] quinolin-4（SH ）-ones and DPP-4. The hydrogen bonding and hydrophobic interactions between inhibitors and adjacent residues are analyzed and discussed. The cal- culated binding free energies using MM-PBSA method are consistent with the experimental data. The van der Waals interaction between key residues of DPP-4 and inhibitors has larger contribution to total energy and can distinguish the binding affinity of four inhibitors.