Inclusion of Solvation in Ligand Binding Free Energy Calculations Using the Generalized-Born Model
Inclusion of Solvation in Ligand Binding Free Energy Calculations Using the Generalized-Born Model
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DOI：
10.1021/ja984102p
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发表时间：
1999-08
影响因子：
15
通讯作者：
X. Zou;and Yaxiong Sun;I. Kuntz
中科院分区：
文献类型：
--
作者：
X. Zou;and Yaxiong Sun;I. Kuntz
解释溶剂对分子相互作用强度的影响一直是分子计算的一个长期问题，特别是对于基于结构的药物设计。在这里，我们探讨了广义玻恩（GB/SA）模型的溶剂化（斯蒂尔，W。C.的; Tempczyk，A.;霍利河C.的; Hendrickson，T. J. Am. 1990，112，6127−9）计算配体-受体结合能。GB/SA方法允许估计静电、货车范德华和疏水对结合自由能的贡献。GB/SA公式在这些计算中提供了计算速度和准确性之间的良好平衡。推导了结合自由能的计算公式。我们还开发了一种程序，以惩罚任何未被占用的嵌入空间，可能会形成之间的配体和受体在对接过程中。为了提高计算速度，蛋白质对静电屏蔽的贡献被预先计算并存储在网格上。精炼...
Accounting for the effect of solvent on the strength of molecular interactions has been a long-standing problem for molecular calculations in general and for structure-based drug design in particular. Here, we explore the generalized-Born (GB/SA) model of solvation (Still, W. C.; Tempczyk, A.; Hawley, R. C.; Hendrickson, T. J. Am. Chem. Soc. 1990, 112, 6127−9) to calculate ligand−receptor binding energies. The GB/SA approach allows for the estimation of electrostatic, van der Waals, and hydrophobic contributions to the free energy of binding. The GB/SA formulation provides a good balance between computational speed and accuracy in these calculations. We have derived a formula to estimate the binding free energy. We have also developed a procedure to penalize any unoccupied embedded space that might form between the ligand and the receptor during the docking process. To improve the computational speed, the protein contribution to the electrostatic screening is precalculated and stored on a grid. Refinement...