Binding mode prediction of cytochrome P450 and thymidine kinase protein-ligand complexes by consideration of water and rescoring in automated docking
Binding mode prediction of cytochrome P450 and thymidine kinase protein-ligand complexes by consideration of water and rescoring in automated docking
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DOI：
10.1021/jm049650u
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发表时间：
2005-04-07
影响因子：
7.3
通讯作者：
Vermeulen, NPE
中科院分区：
文献类型：
--
作者：
de Graaf, C;Pospisil, P;Vermeulen, NPE
流行的对接程序AutoDock，FlexX和GOLD被用来预测晶体复合物中配体的结合模式，包括X射线水分子或计算预测的水分子。使用两种不同酶系统的同工酶，即细胞色素P450（n = 19）和胸苷激酶（n = 19），以及三种不同的“水”情况：对接（i）到无水活性位点，（ii）到含有结晶水分子的活性位点，和（iii）到含有水分子的活性位点预测的一种新的方法的基础上的程序网格。对接准确度确定的均方根偏差（RMSD）的准确性，并在新定义的配体催化位点预测（CSP）的准确性。考虑到X射线和预测的水分子以及随后使用SCORE评分功能对所有溶液（由所有三个对接程序生成）进行合并和重新评分，在RMSD和CSP准确性方面显著提高了结合模式的预测质量。
The popular docking programs AutoDock, FlexX, and GOLD were used to predict binding modes of ligands in crystallographic complexes including X-ray water molecules or computationally predicted water molecules. Isoenzymes of two different enzyme systems were used, namely cytochromes P450 (n = 19) and thymidine kinases (n = 19) and three different "water" scenarios: i.e., docking (i) into water-free active sites, (ii) into active sites containing crystallographic water molecules, and (iii) into active sites containing water molecules predicted by a novel approach based on the program GRID. Docking accuracies were determined in terms of the root-mean-square deviation (RMSD) accuracy and, newly defined, in terms of the ligand catalytic site prediction (CSP) accuracy. Consideration of both X-ray and predicted water molecules and the subsequent pooling and rescoring of all solutions (generated by all three docking programs) with the SCORE scoring function significantly improved the quality of prediction of the binding modes both in terms of RMSD and CSP accuracy.