Further development and validation of empirical scoring functions for structure-based binding affinity prediction
Further development and validation of empirical scoring functions for structure-based binding affinity prediction
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DOI：
10.1023/a:1016357811882
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发表时间：
2002-01-01
影响因子：
3.5
通讯作者：
Wang, SM
中科院分区：
文献类型：
--
作者：
Wang, RX;Lai, LH;Wang, SM
已经开发出新的经验性评分函数，用于估算具有已知三维结构的特定蛋白质 - 配体复合物的结合亲和力。这些评分函数包含考虑范德华相互作用、氢键、变形罚分和疏水效应的项。一个特点是，已经采用三种不同算法来计算疏水效应项，从而产生三个并行的评分函数。所有这三个评分函数都通过对200个蛋白质 - 配体复合物的多元回归分析进行校准，它们对整个训练集的结合自由能的重现标准偏差分别为2.2千卡/摩尔、2.1千卡/摩尔和2.0千卡/摩尔。这三个评分函数进一步组合成一个一致性评分函数X - CSCORE。当在一组独立的30个蛋白质 - 配体复合物上进行测试时，X - CSCORE能够以2.2千卡/摩尔的标准偏差预测它们的结合自由能。还研究了X - CSCORE在分子对接中的潜在应用。我们的结果表明，与用于分子对接的常规力场计算相比，这个一致性评分函数显著提高了对接准确性。
New empirical scoring functions have been developed to estimate the binding affinity of a given protein-ligand complex with known three-dimensional structure. These scoring functions include terms accounting for van der Waals interaction, hydrogen bonding, deformation penalty, and hydrophobic effect. A special feature is that three different algorithms have been implemented to calculate the hydrophobic effect term, which results in three parallel scoring functions. All three scoring functions are calibrated through multivariate regression analysis of a set of 200 protein-ligand complexes and they reproduce the binding free energies of the entire training set with standard deviations of 2.2 kcal/mol, 2.1 kcal/mol, and 2.0 kcal/mol, respectively. These three scoring functions are further combined into a consensus scoring function, X-CSCORE. When tested on an independent set of 30 protein-ligand complexes, X-CSCORE is able to predict their binding free energies with a standard deviation of 2.2 kcal/mol. The potential application of X-CSCORE to molecular docking is also investigated. Our results show that this consensus scoring function improves the docking accuracy considerably when compared to the conventional force field computation used for molecular docking.