应用MMPBSA方法研究CDK2活性口袋内溶剂水分子对C体结合自由能.pdfVIP

2009 年第 67 卷 化 学 学 报 Vol. 67, 2009 第 3 期, 255～260 ACTA CHIMICA SINICA No. 3, 255～260 ·研究论文· 应用 MM/PBSA 方法研究 CDK2 活性口袋内溶剂水分子对 CDK2-配体 结合自由能的影响 杨丽君 a,b 贾 若 a 杨胜勇*,a (a 四川大学华西医院 生物治疗国家重点实验室 成都 610041) (b 西华师范大学化学化工学院 南充 637002) 摘要 应用 MM/PBSA 方法研究了 CDK2 活性口袋内溶剂水分子对 CDK2-配体结合自由能的影响. 结果表明, 活性口 袋内溶剂水分子对 CDK2-配体相互作用自由能有一定的贡献, 其贡献的大小随配体不同而有所差异, 导致这种差异的 主要原因是活性位点内溶剂水分子与蛋白残基和配体之间形成了不同的氢键相互作用网络. 关键词 MM/PBSA; CDK2; 结合自由能; 溶剂水分子; 分子动力学 Influence of the Solvent Water Molecules at the Active Site of CDK2 on the Binding Free Energy of CDK2-ligand Complexes: an MM/PBSA Study Yang, Lijuna,b Jia, Ruoa Yang, Shengyong*,a a ( State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041) (b College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637002) Abstract An MM/PBSA method has been used to investigate the influence of the solvent water molecules at the active site of CDK2 on the binding free energy of CDK2-ligand complexes. The results show that the solvent water molecules at the active site of CDK2 have some contribution to the binding free energy of CDK2-ligand complex. However, the magnitude of contribution depends on the characteristic of the corre- sponding ligand. The difference of the contribution is mainly due to the different hydrogen bonding interac-