Assessing the performance of the molecular mechanics/Poisson Boltzmann surface area and molecular mechanics/generalized Born surface area methods. II. The accuracy of ranking poses generated from docking.
Assessing the performance of the molecular mechanics/Poisson Boltzmann surface area and molecular mechanics/generalized Born surface area methods. II. The accuracy of ranking poses generated from docking.
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DOI：
10.1002/jcc.21666
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发表时间：
2011-04-15
影响因子：
3
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Hou, Tingjun;Wang, Junmei;Li, Youyong;Wang, Wei
在分子对接中，开发一种准确的评分函数来进行高通量筛选（HTS）是一个挑战。在常用的对接软件包中，大多数评分函数都是为了提高计算效率而采用许多近似的方法来实现的，这就牺牲了预测的准确性。在当今先进的技术和强大的计算硬件的条件下，分子力学/泊松-玻尔兹曼表面积（MM/PBSA）和分子力学/广义玻恩表面积（MM/GBSA）等严格的评分函数在分子对接研究中是可行的。在此，我们系统地研究了MM/PBSA和MM/GBSA的性能，以确定正确的结合构象并预测98种蛋白质/配体复合物的结合自由能。比较研究表明，MM/GBSA（69.4%）在识别正确的结合构象方面优于MM/PBSA（45.5%）和许多流行的评分函数。此外，我们发现分子动力学（MD）模拟对于某些系统识别正确的结合构象是必要的。基于我们的研究结果，我们提出了MM/GBSA预测结合构象的准则。然后，我们测试了MM/GBSA和MM/PBSA的性能，以重现98个蛋白质配体复合物的结合自由能。MM/GBSA内部介电2.0模型的Spearman相关系数为0.66，优于MM/PBSA（0.49）和几乎所有用于分子对接的评分函数。综上所述，MM/GBSA在结合位姿预测和结合自由能估计方面都表现良好，并且可以有效地对其他不太准确的评分函数产生的顶击位姿进行重新评分。
In molecular docking, it is challenging to develop a scoring function which is accurate to conduct high throughput screenings (HTS). Most scoring functions implemented in popular docking software packages were developed with many approximations for computational efficiency, which sacrifices the accuracy of prediction. With advanced technology and powerful computational hardware nowadays, it is feasible to use rigorous scoring functions, such as Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA) and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) in molecular docking studies. Here we systematically investigated the performance of MM/PBSA and MM/GBSA to identify the correct binding conformations and predict the binding free energies for 98 protein/ligand complexes. Comparison studies showed that MM/GBSA (69.4%) outperformed MM/PBSA (45.5%) and many popular scoring functions to identify the correct binding conformations. Moreover, we found that molecular dynamics (MD) simulations are necessary for some systems to identify the correct binding conformations. Based on our results, we proposed the guideline for MM/GBSA to predict the binding conformations. We then tested the performance of MM/GBSA and MM/PBSA to reproduce the binding free energies of the 98 protein-ligand complexes. The best prediction of MM/GBSA model with internal dielectric 2.0, produced a Spearman correlation coefficient of 0.66, which is better than MM/PBSA (0.49) and almost all scoring functions used in molecular docking. In summary, MM/GBSA performs well for both binding pose predictions and binding free energy estimations and is efficient to re-score the top-hit poses produced by other less accurate scoring functions.
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影响因子：
7.3
作者：
Kuhn, B;Gerber, P;Stahl, M
通讯作者：
Stahl, M
影响因子：
7.3
作者：
Muegge, I;Martin, YC
通讯作者：
Martin, YC
影响因子：
3
作者：
Gohlke, H;Case, DA
通讯作者：
Case, DA
影响因子：
0.8
作者：
Batsanov, SS
通讯作者：
Batsanov, SS
影响因子：
3
作者：
Duan, Y;Wu, C;Kollman, P
通讯作者：
Kollman, P