QM/MM在计算DNA与配体评分函数的准确性研究

Evaluation of QM/MM Scoring Functions in DNA-ligand Complexes

目的:评估QM/MM方法和Surflex-Dock分子对接程序对DNA-配体复合物模拟的准确性。方法:从蛋白质数据库(Protein Data Bank)下载DNA-配体复合物的三维结构,利用计算机辅助药物设计的分子对接程序Surflex-Dock模拟出147个诱饵化合物(decoys)并计算其结合分数(binding score)。然后将得出的分数与从QM/MM计算的结合能力以Z-score和辨别力(DP)作比较。从而评估Surflex-Dock和QM/MM的准确性。结果:Surflex-Dock的DPi值比QM/MM高,显示Surflex-Dock的辨别力较低。结论:因QM/MM计算速度慢,本研究认为Surflex-Dock可用作快速虚拟筛选,而较准确的QM/MM则适合用于对拥有较高结合分数的化合物进行再评分(rescoring)。

Objective： Assess the accuracy of Surflex-Dock and QM/MM scoring functions on DNA-ligand complexes. Methods： Three-dimensional structures of DNA-ligand complexes were downloaded from Protein Data Bank. The docking software, Surflex-Dock was used to generate and calculate the binding scores of 147 decoys. QM/MM scoring functions were employed to calculate the binding energies of these decoys. Z-scores and discriminative powers（DPi） were then calculated for both Surflex-Dock and QM/MM. Results： Surflex-Dock obtained a higher DPi value than QM/MM, this indicates that QM/MM has a higher discriminative power than Surflex-Dock. However, the computational demand of QM/MM is much higher than Surflex-Dock. Conclusion： Surflex-Dock is suitable for the use of virtual screening and the more accurate QM/MM calculations may serve as a rescoring method.