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Precision Drug, Precision Design

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Front. Pharmacol. | doi: 10.3389/fphar.2018.01463

An improved receptor-based pharmacophore generation algorithm guided by atomic chemical characteristics and hybridization types

 Gaoqi He1, Bojie Gong1, Jianqiang Li1, Yiping Song1,  Shiliang Li1 and Xingjian Lu1*
  • 1East China University of Science and Technology, China

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 3Å 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.

Keywords: receptor-based pharmacophore generation, hybridization type, aromatic ring characteristic extraction, Space constraint, DUD dataset testing

Received: 28 Jul 2018; Accepted: 29 Nov 2018.

Edited by:

Jianfeng Pei, Peking University, China

Reviewed by:

Sergei Noskov, University of Calgary, Canada
Darren Fayne, School of Biochemistry and Immunology, Trinity College Dublin, Ireland  

Copyright: © 2018 He, Gong, Li, Song, Li and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Xingjian Lu, East China University of Science and Technology, Shanghai, China, luxj@ecust.edu.cn