Version 1
: Received: 5 October 2019 / Approved: 7 October 2019 / Online: 7 October 2019 (12:33:33 CEST)
How to cite:
Nain, Z.; Bin Sayed, S.; Karim, M.M.; Islam, M.A.; Adhikari, U.K. Energy-Optimized Pharmacophore Coupled Virtual Screening in the Discovery of Quorum Sensing Inhibitors of LasR Protein of Pseudomonas aeruginosa. Preprints2019, 2019100074. https://doi.org/10.20944/preprints201910.0074.v1
Nain, Z.; Bin Sayed, S.; Karim, M.M.; Islam, M.A.; Adhikari, U.K. Energy-Optimized Pharmacophore Coupled Virtual Screening in the Discovery of Quorum Sensing Inhibitors of LasR Protein of Pseudomonas aeruginosa. Preprints 2019, 2019100074. https://doi.org/10.20944/preprints201910.0074.v1
Nain, Z.; Bin Sayed, S.; Karim, M.M.; Islam, M.A.; Adhikari, U.K. Energy-Optimized Pharmacophore Coupled Virtual Screening in the Discovery of Quorum Sensing Inhibitors of LasR Protein of Pseudomonas aeruginosa. Preprints2019, 2019100074. https://doi.org/10.20944/preprints201910.0074.v1
APA Style
Nain, Z., Bin Sayed, S., Karim, M.M., Islam, M.A., & Adhikari, U.K. (2019). Energy-Optimized Pharmacophore Coupled Virtual Screening in the Discovery of Quorum Sensing Inhibitors of LasR Protein of <em>Pseudomonas aeruginosa</em>. Preprints. https://doi.org/10.20944/preprints201910.0074.v1
Chicago/Turabian Style
Nain, Z., Md. Ariful Islam and Utpal Kumar Adhikari. 2019 "Energy-Optimized Pharmacophore Coupled Virtual Screening in the Discovery of Quorum Sensing Inhibitors of LasR Protein of <em>Pseudomonas aeruginosa</em>" Preprints. https://doi.org/10.20944/preprints201910.0074.v1
Abstract
Pseudomonas aeruginosa is an emerging opportunistic pathogen responsible for cystic fibrosis and nosocomial infections. In addition, empirical treatments are become inefficient due to their multiple-antibiotic resistance and extensive colonizing ability. Quorum sensing (QS) plays a vital role in the regulation of virulence factors in P. aeruginosa. Attenuation of virulence by QS inhibition could be an alternative and effective approach to control infections. Therefore, we sought to discover new QS inhibitors (QSIs) against LasR receptor in P. aeruginosa using chemoinformatics. Initially, a structure-based high-throughput virtual screening was performed using the LasR active site that identified 61404 relevant molecules. E-pharmacophore (ADAHH) screening of these molecules rendered 72 QSI candidates. In standard-precision docking, only 7 compounds were found as potential QSIs due to their higher binding affinity to LasR receptor (-7.53 to -10.32 kcal/mol compared to -7.43 kcal/mol of native ligands). The ADMET properties of these compounds were suitable to be QSIs. Later, extra-precision docking and binding energy calculation suggested ZINC19765885 and ZINC72387263 as the most promising QSIs. The dynamic simulation of the docked complexes showed good binding stability and molecular interactions. The current study suggested that these two compounds could be used in P. aeruginosa QS inhibition to combat bacterial infections.
Keywords
Pseudomonas aeruginosa; Quorum sensing; Virtual screening; E-pharmacophore; Drug discovery.
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
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.
