论文部分内容阅读
通过分子对接、分子动力学(MD)模拟以及成键自由能分析方法,从原子水平上模拟研究了3种1,7-二氮杂咔唑衍生物(分别记为M1、M2和M3)与ACh E的结合模式及相互作用机理,分析和讨论了研究体系的静电相互作用和范德华相互作用(vd W)。用MM-PBSA方法计算的3种抑制剂与ACh E之间的结合自由能与抑制剂的实验生物活性数据(IC50值)相对应。分析结果表明,残基S286与抑制剂之间形成的氢键作用有利于抑制剂与ACh E之间的结合。范德华相互作用,尤其是抑制剂与关键残基W279和Y334的作用,对抑制剂与ACh E之间的结合自由能有较大的贡献,在区分抑制剂M1(或M2)和M3的生物活性上发挥着重要的作用。
By means of molecular docking, molecular dynamics (MD) simulation and bond free energy analysis, three kinds of 1,7-diazacarbazole derivatives (M1, M2 and M3 respectively) ACh E binding mode and interaction mechanism, the electrostatic interaction and van der Waals interaction (vd W) of the research system were analyzed and discussed. The free energy of binding between the 3 inhibitors calculated by the MM-PBSA method and ACh E corresponds to the experimental bioactivity data of the inhibitor (IC50 value). The results showed that the hydrogen bond formed between the residue S286 and the inhibitor favored the binding between the inhibitor and ACh E. Van der Waal’s interaction, in particular the inhibitor and the key residues W279 and Y334, contributes significantly to the free energy of binding between the inhibitor and AChE, and in distinguishing the bioactivities of inhibitors M1 (or M2) and M3 Play an important role.