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为了说明V82A和L90M变异对蛋白酶(PR)和茚地那韦(IDV)复合物的影响,进行了5.5ns的MD模拟.用MM-PBSA方法计算了体系的结合自由能,计算和实验结果一致.分解自由能为不同能量项说明,这两个变异引起熵的贡献变化大于焓的贡献变化.分解自由能到每个残基说明Wild,V82A和L90M具有相似的结合模式,结合能的贡献主要来源于A28/A28’,I50/I50’和I84/I84’这六个残基组,详细分析了Wild和IDV的结合模式,对比分析了V82A和L90M变异引起结合模式的细小变化.V82A变异引起结合模式的变化是由于变异后位阻减小导致的.L90M变异引起D25和L90间的作用增强并引起结合模式的细小变化.研究结果有助于更好地理解变异对抑制剂和HIV-1PR结合模式的影响,并可以用来帮助设计更高效的PR抑制剂.
In order to illustrate the effect of V82A and L90M mutations on protease (PR) and indinavir (IDV) complexes, a 5.5-ns MD simulation was performed using the MM-PBSA method to calculate the binding energy of the system, which is consistent with experimental results .Fractional free energy can be explained by different energy terms, and these two variations cause the contribution of entropy change to be larger than the contribution of enthalpy change.Decomposition of free energy to each residue indicates that Wild, V82A and L90M have similar binding patterns and binding energy contribution mainly Derived from the six residue groups A28 / A28 ’, I50 / I50’ and I84 / I84 ’, analyzed in detail the binding patterns of Wild and IDV, and compared and analyzed the small changes of the binding patterns caused by V82A and L90M mutations. The change in binding pattern is due to a reduction in steric hindrance due to mutation.The L90M mutation causes an increase in the interaction between D25 and L90 and causes a small change in binding pattern.These results contribute to a better understanding of the effect of variation on inhibitor and HIV- The impact of binding patterns and can be used to help design more potent PR inhibitors.