Department of Chemistry, Moscow State University, Leninskie Gory 1/3, Moscow 119991, Russia.
Chem Biol Drug Des. 2011 Sep;78(3):378-90. doi: 10.1111/j.1747-0285.2011.01159.x. Epub 2011 Jul 29.
Comparative assessment of nine different scoring functions (OpenEye and Tripos implementation) applied to structure-based virtual screening based on rigid docking of the pregenerated conformations library of glycogen synthase kinase 3β (GSK-3β) inhibitors has been carried out. The functions studied belong to the following types: Gaussian (Chemgauss3, Shapegauss), empirical (Chemscore, OEChemscore, Piecewise Linear Potential, Screenscore), force field-based (D_score and G_score), and potential of mean force (PMF_score). Overall enrichment of the large true inhibitors set against the set of true non-inhibitors, Directory of Useful Decoys (DUD), cyclin-dependent kinase 2 subset, and NCI Diversity Set was evaluated by means of ROC (receiver operating characteristic) method. According to this analysis, scoring function Chemscore leads to the best enrichment of the inhibitors whereas the best early enrichment of the actives may be obtained with the help of Chemgauss3 function as estimated by BEDROC (Boltzmann-enhanced discrimination of ROC) metrics.
已对基于刚性对接糖原合酶激酶 3β（GSK-3β）抑制剂预生成构象文库的结构基虚拟筛选应用的九种不同评分函数（OpenEye 和 Tripos 实现）进行了比较评估。所研究的函数属于以下类型：高斯（Chemgauss3、Shapegauss）、经验（Chemscore、OEChemscore、分段线性势能、Screenscore）、基于力场（D_score 和 G_score）和平均势（PMF_score）。通过 ROC（接收者操作特征）方法评估了大型真实抑制剂集相对于有用诱饵目录（DUD）、细胞周期蛋白依赖性激酶 2 子集和 NCI 多样性集的整体富集情况。根据该分析，评分函数 Chemscore 导致抑制剂的最佳富集，而 Chemgauss3 函数的 BEDROC（ROC 的玻尔兹曼增强判别）指标估计表明，该函数可用于获得活性物质的最佳早期富集。
