Tanchuk Vsevolod Yu, Tanin Volodymyr O, Vovk Andriy I, Poda Gennady
Department of Bioorganic Mechanisms, Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, 1 Murmanska Street-94, Kyiv, 02660, Ukraine.
Drug Discovery Program, Ontario Institute for Cancer Research (OICR), 661 University Avenue, Suite 510, Toronto, ON, Canada, M5G 0A3.
Chem Biol Drug Des. 2016 Apr;87(4):618-25. doi: 10.1111/cbdd.12697. Epub 2015 Dec 29.
Automated docking is one of the most important tools for structure-based drug design that allows prediction of ligand binding poses and also provides an estimate of how well small molecules fit in the binding site of a protein. A new scoring function based on AutoDock and AutoDock Vina has been introduced. The new hybrid scoring function is a linear combination of the two scoring function components derived from a multiple linear regression fitting procedure. The scoring function was built on a training set of 2412 protein-ligand complexes from pdbbind database (www.pdbbind.org.cn, version 2012). A test set of 313 complexes that appeared in the 2013 version was used for validation purposes. The new hybrid scoring function performed better than the original functions, both on training and test sets of protein-ligand complexes, as measured by the non-parametric Pearson correlation coefficient, R, mean absolute error (MAE), and root-mean-square error (RMSE) between the experimental binding affinities and the docking scores. The function also gave one of the best results among more than 20 scoring functions tested on the core set of the pdbbind database. The new AutoDock hybrid scoring function will be implemented in modified version of AutoDock.
自动对接是基于结构的药物设计中最重要的工具之一，它能够预测配体的结合姿势，还能估计小分子在蛋白质结合位点的契合程度。一种基于AutoDock和AutoDock Vina的新评分函数已经被引入。这种新的混合评分函数是通过多元线性回归拟合程序从两个评分函数组件中得到的线性组合。该评分函数基于来自pdbbind数据库（www.pdbbind.org.cn，2012版）的2412个蛋白质-配体复合物训练集构建而成。2013版中出现的313个复合物测试集用于验证目的。通过实验结合亲和力与对接分数之间的非参数皮尔逊相关系数R、平均绝对误差（MAE）和均方根误差（RMSE）衡量，新的混合评分函数在蛋白质-配体复合物的训练集和测试集上都比原始函数表现更好。在对pdbbind数据库核心集测试的20多个评分函数中，该函数也给出了最佳结果之一。新的AutoDock混合评分函数将在AutoDock的修改版本中实现。
