Borodina Yulia V, Bolton Evan, Fontaine Fabien, Bryant Stephen H
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20894, USA.
J Chem Inf Model. 2007 Jul-Aug;47(4):1428-37. doi: 10.1021/ci7000956. Epub 2007 Jun 15.
The size of conformational ensembles required for regular coverage of the conformational space of druglike molecules was examined. Using the conformer generation program Omega, the number of regularly distributed conformers (NRC) of flexible compounds was determined as a function of the root-mean-square deviation (RMSD) resolution of coverage. A regression equation was developed predicting the NRC of a molecule as a function of RMSD. The model yielded R(2) of 0.91 for both training and test sets, which consisted of 3414 and 3352 compounds, respectively. Utilizing 14 504 ligands from the Protein Data Bank with experimentally determined 3-D conformations, the regression equation was applied to the estimation of the NRC and the success rate of reproduction of experimental conformations from a theoretical conformation ensemble as a function of RMSD and flexibility was explored.
研究了对类药物分子构象空间进行规则覆盖所需的构象集合大小。使用构象生成程序Omega，确定了柔性化合物规则分布构象（NRC）的数量与覆盖的均方根偏差（RMSD）分辨率的函数关系。建立了一个回归方程，预测分子的NRC作为RMSD的函数。该模型对训练集和测试集的R(2)均为0.91，训练集和测试集分别包含3414个和3352个化合物。利用蛋白质数据库中14504个具有实验确定三维构象的配体，将回归方程应用于NRC的估计，并探索了从理论构象集合中再现实验构象的成功率与RMSD和柔性的函数关系。
