Department of Mathematics, Moscow Institute of Physics and Technology , Moscow 117303, Russia.
Faculty of Fundamental Medicine, Moscow State University , Moscow 119991, Russia.
J Chem Inf Model. 2015 Oct 26;55(10):2121-37. doi: 10.1021/acs.jcim.5b00158. Epub 2015 Oct 8.
We analyzed the frequency with which intraligand contacts occurred in a set of 1300 protein-ligand complexes [ Plewczynski et al. J. Comput. Chem. 2011 , 32 , 742 - 755 .]. Our analysis showed that flexible ligands often form intraligand hydrophobic contacts, while intraligand hydrogen bonds are rare. The test set was also thoroughly investigated and classified. We suggest a universal method for enhancement of a scoring function based on a potential of mean force (PMF-based score) by adding a term accounting for intraligand interactions. The method was implemented via in-house developed program, utilizing an Algo_score scoring function [ Ramensky et al. Proteins: Struct., Funct., Genet. 2007 , 69 , 349 - 357 .] based on the Tarasov-Muryshev PMF [ Muryshev et al. J. Comput.-Aided Mol. Des. 2003 , 17 , 597 - 605 .]. The enhancement of the scoring function was shown to significantly improve the docking and scoring quality for flexible ligands in the test set of 1300 protein-ligand complexes [ Plewczynski et al. J. Comput. Chem. 2011 , 32 , 742 - 755 .]. We then investigated the correlation of the docking results with two parameters of intraligand interactions estimation. These parameters are the weight of intraligand interactions and the minimum number of bonds between the ligand atoms required to take their interaction into account.
我们分析了 1300 个蛋白质-配体复合物[Plewczynski 等人，J. Comput. Chem. 2011, 32, 742-755]中配体内部接触的频率。我们的分析表明，柔性配体通常形成配体内部疏水接触，而配体内部氢键则很少见。测试集也经过了彻底的研究和分类。我们建议了一种基于平均力势（PMF 基评分）的评分函数增强的通用方法，通过添加一个考虑配体内部相互作用的项来实现。该方法通过内部开发的程序实现，利用基于 Tarasov-Muryshev PMF 的 Algo_score 评分函数[Ramensky 等人，Proteins: Struct., Funct., Genet. 2007, 69, 349-357]。我们发现，在 1300 个蛋白质-配体复合物的测试集中，该评分函数的增强显著提高了柔性配体的对接和评分质量[Plewczynski 等人，J. Comput. Chem. 2011, 32, 742-755]。然后，我们研究了对接结果与配体内部相互作用估计的两个参数之间的相关性。这两个参数是配体内部相互作用的权重和考虑其相互作用所需的配体原子之间的最小键数。
