文献类型：期刊文献

英文题名：An Improved Receptor-Based Pharmacophore Generation Algorithm Guided by Atomic Chemical Characteristics and Hybridization Types

作者：He, Gaoqi[1,3];Gong, Bojie[1];Li, Jianqiang[1];Song, Yiping[1];Li, Shiliang[2];Lu, Xingjian[1,2]

机构：[1]East China Univ Sci & Technol, Dept Comp Sci & Engn, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[3]East China Normal Univ, Sch Comp Sci & Software Engn, Shanghai, Peoples R China

年份：2018

卷号：9

外文期刊名：FRONTIERS IN PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000453398900001)】；

基金：This work was supported by National Key Research and Development Program [2016YFA0502304]; National Natural Science Foundation of China [61602175, 81803437, 81825020]; the Open Project Program of State Key Laboratory of Virtual Reality Technology and Systems, Beihang University(No. VRLAB2018B12).

语种：英文

外文关键词：receptor-based pharmacophore generation; hybridization type; aromatic ring characteristic extraction; space constraint; DUD dataset testing

摘要：Pharmacophore-based virtual screening is an important and leading compound discovery method. However, current pharmacophore generation algorithms suffer from difficulties, such as ligand-dependent computation and massive extractive chemical features. On the basis of the features extracted by the five probes in Pocket v.3, this paper presents an improved receptor-based pharmacophore generation algorithm guided by atomic chemical characteristics and hybridization types. The algorithm works under the constraint of receptor atom hybridization types and space distance. Four chemical characteristics (H-A, H-D, and positive and negative charges) were extracted using the hybridization type of receptor atoms, and the feature point sets were merged with 3 A space constraints. Furthermore, on the basis of the original extraction of hydrophobic characteristics, extraction of aromatic ring chemical characteristics was achieved by counting the number of aromatics, searching for residual base aromatic ring, and determining the direction of aromatic rings. Accordingly, extraction of six kinds of chemical characteristics of the pharmacophore was achieved. In view of the pharmacophore characteristics, our algorithm was compared with the existing LigandScout algorithm. The results demonstrate that the pharmacophore possessing six chemical characteristics can be characterized using our algorithm, which features fewer pharmacophore characteristics and is ligand independent. The computation of many instances from the directory of useful decoy dataset show that the active molecules and decoy molecules can be effectively differentiated through the presented method in this paper.