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Title: Reduction of false positives in structure-based virtual screening when receptor plasticity is considered
Authors: Awuni, Yaw
Mu, Yuguang
Keywords: DRNTU::Science::Biological sciences::Molecular biology
Issue Date: 2015
Source: Awuni, Y., & Mu, Y. (2015). Reduction of false positives in structure-based virtual screening when receptor plasticity is considered. Molecules, 20(3), 5152-5164.
Series/Report no.: Molecules
Abstract: Structure-based virtual screening for selecting potential drug candidates is usually challenged by how numerous false positives in a molecule library are excluded when receptor plasticity is considered. In this study, based on the binding energy landscape theory, a hypothesis that a true inhibitor can bind to different conformations of the binding site favorably was put forth, and related strategies to defeat this challenge were devised; reducing false positives when receptor plasticity is considered. The receptor in the study is the influenza A nucleoprotein, whose oligomerization is a requirement for RNA binding. The structural flexibility of influenza A nucleoprotein was explored by molecular dynamics simulations. The resultant distinctive structures and the crystal structure were used as receptor models in docking exercises in which two binding sites, the tail-loop binding pocket and the RNA binding site, were targeted with the Otava PrimScreen1 diversity-molecule library using the GOLD software. The intersection ligands that were listed in the top-ranked molecules from all receptor models were selected. Such selection strategy successfully distinguished high-affinity and low-affinity control molecules added to the molecule library. This work provides an applicable approach for reducing false positives and selecting true ligands from molecule libraries.
ISSN: 1420-3049
DOI: 10.3390/molecules20035152
Rights: © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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