Table of Contents
ISRN Bioinformatics
Volume 2013 (2013), Article ID 640518, 12 pages
Research Article

Discovery of YopE Inhibitors by Pharmacophore-Based Virtual Screening and Docking

Department of Chemical Engineering, Boğaziçi University, 34342 Istanbul, Turkey

Received 12 June 2013; Accepted 28 August 2013

Academic Editors: Z. Gáspári, D. Labudde, and D. A. McClellan

Copyright © 2013 Gizem Ozbuyukkaya et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Gram-negative bacteria Yersinia secrete virulence factors that invade eukaryotic cells via type III secretion system. One particular virulence member, Yersinia outer protein E (YopE), targets Rho family of small GTPases by mimicking regulator GAP protein activity, and its secretion mainly induces cytoskeletal disruption and depolymerization of actin stress fibers within the host cell. In this work, potent drug-like inhibitors of YopE are investigated with virtual screening approaches. More than 500,000 unique small molecules from ZINC database were screened with a five-point pharmacophore, comprising three hydrogen acceptors, one hydrogen donor, and one ring, and derived from different salicylidene acylhydrazides. Binding modes and features of these molecules were investigated with a multistep molecular docking approach using Glide software. Virtual screening hits were further analyzed based on their docking score, chemical similarity, pharmacokinetic properties, and the key Arg144 interaction along with other active site residue interactions with the receptor. As a final outcome, a diverse set of ligands with inhibitory potential were proposed.