【摘要】 采用基于线性响应近似的自由能计算方法计算了一类hydroxamate抑制剂和MMP 2的绝对结合自由能 .计算中 ,催化锌离子和MMP 2以及配体之间采用了非键模型 .分子动力学模拟结果显示 ,采用非键模型时 ,催化Zn离子采用五配位的形式 ,但配位键的形式和初始结构比较有很大的差别 .通过拟合 ,分别得到了单参数、双参数以及三参数的自由能预测模型 ,其中 ,含有常数校正项的三参数模型具有最佳的预测能力 ,预测自由能和实际自由能之间平均绝对误差仅为 2 .38kJ/mol.更多还原

【Abstract】 The absolute binding affinities of a series of hydroxamate inhibitors with MMP-2 were evaluated by molecular dynamics (MD) simulations with a linear response approach. During MD simulations, a nonbonded model for the catalytic zinc center was used to represent the interactions between zinc center and enzyme/inhibitor. The trajectories from MD simulation show that using the nonbonded model the catalytic zinc ion adopts five coordination number, but the coordination form exists large difference with that of the initial model. After fittings, the models with one parameter, two parameters and three parameters were obtained. The calculated results indicate that the three-parameter model with a constant term bears the best predicting ability. The best model yields an average error of 2.38 kJ/mol for the eight binding affinities of hydroxamtes.更多还原