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Front. Chem. | doi: 10.3389/fchem.2018.00138

Reverse screening methods to search for the protein targets of chemopreventive compounds

Hongbin Huang1,  Guigui Zhang1, Yuquan Zhou1, Chenru Lin1, Suling Chen1, Yutong Lin1, Shangkang Mai1 and  Zunnan Huang1*
  • 1Guangdong Medical University, China

This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and grasp the types of calculations used in protein target fishing. In addition, we review the main features of these methods, programs and databases and provide a variety of examples illustrating the application of one or a combination of reverse screening methods for accurate target prediction.

Keywords: drug design, Reverse screening, shape similarity, Pharmacophore Modeling, Reverse docking, methodology, Online service, Screening Databases

Received: 08 Feb 2018; Accepted: 09 Apr 2018.

Edited by:

Daniela Schuster, Paracelsus Medizinische Privatuniversität, Salzburg, Austria

Reviewed by:

Marco Tutone, Universita' di Palermo, Italy
Francesco Ortuso, Università degli studi Magna Græcia di Catanzaro, Italy  

Copyright: © 2018 Huang, Zhang, Zhou, Lin, Chen, Lin, Mai and Huang. 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 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: Prof. Zunnan Huang, Guangdong Medical University, Dongguan, China,