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采用分子对接,分子动力学(MD)模拟和分子力学/泊松-波尔兹曼溶剂可有面积方法与分子力学/广义伯恩溶剂可及面积方法(MM-PBSA/MM-GBSA),预测两种N-取代吡咯衍生物与HIV-1跨膜蛋白gp41疏水口袋的结合模式与作用机理.分子对接采用多种受体构象,并从结果中选取几种可能的结合模式进行MD模拟,然后通过MM-PBSA计算结合能的方法识别最优的结合模式.MM-PBSA计算结果表明,范德华相互作用是结合的主要驱动力,而极性相互作用决定了配体在结合过程中的取向.进一步的结合能分解显示,配体的羧基与gp41残基Arg579的静电相互作用对结合有重要贡献.上述工作为进一步优化N-取代吡咯衍生物类的HIV-1融合抑制剂建立了良好的理论基础。
MM-PBSA / MM-GBSA) was used to predict the molecular weight of the samples by molecular docking (MD) simulation and molecular mechanics / Poisson-Boltzmann solvent area method and molecular mechanics / Two N-substituted Pyrrole Derivatives and HIV-1 Transmembrane Protein gp41 Hydrophobic Pocket Binding Mode and Mechanism The molecular docking using a variety of receptor conformation, and from the results of several possible binding modes for MD simulation, and then MM-PBSA calculated the binding energy of the method to identify the optimal binding mode.MM-PBSA calculated results show that Van der Waals interaction is the main driving force of binding, and the polar interaction determines the orientation of the ligand in the binding process further Shows that the electrostatic interaction between the carboxyl group of the ligand and the Arg579 gp41 protein contributes significantly to the binding.The above work provides a good theoretical basis for further optimization of HIV-1 fusion inhibitors of N-substituted pyrrole derivatives .