Ravindranathan Krishna, Tirado-Rives Julian, Jorgensen William L, Guimarães Cristiano R W
Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA.
J Chem Theory Comput. 2011 Dec 13;7(12):3859-3865. doi: 10.1021/ct200565u. Epub 2011 Nov 14.
A variable dielectric model based on residue types for better description of protein-ligand electrostatics in MM-GBSA scoring is reported. The variable dielectric approach provides better correlation with binding data and reduces the score dynamic range, typically observed in the standard MM-GB/SA method. The latter supports the view that exaggerated enthalpic separation between weak and potent compounds due to the lack of shielding effects in the model is greatly responsible for the wide scoring spread.
本文报道了一种基于残基类型的可变介电常数模型，用于在MM-GBSA评分中更好地描述蛋白质-配体静电作用。可变介电常数方法与结合数据具有更好的相关性，并减小了评分动态范围，这在标准MM-GB/SA方法中通常可以观察到。后者支持这样一种观点，即由于模型中缺乏屏蔽效应，导致弱化合物和强化合物之间焓分离过大，这是评分范围广泛的主要原因。
