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Article

Drug Repurposing Targeting Pseudomonas aeruginosa MvfR Using Docking, Virtual Screening, Molecular Dynamics, and Free-Energy Calculations

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UCIBIO/REQUIMTE, BioSIM, Departamento de Medicina, Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
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Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal
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LEPABE Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal
*
Author to whom correspondence should be addressed.
Academic Editor: Abdelwahab Omri
Antibiotics 2022, 11(2), 185; https://doi.org/10.3390/antibiotics11020185
Received: 14 December 2021 / Revised: 26 January 2022 / Accepted: 27 January 2022 / Published: 31 January 2022
Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium responsible for acute and chronic infections in planktonic state or in biofilms. The sessile structures are known to confer physical stability, increase virulence, and work as a protective armor against antimicrobial compounds. P. aeruginosa can control the expression of genes, population density, and biofilm formation through a process called quorum sensing (QS), a rather complex and hierarchical system of communication. A recent strategy to try and overcome bacterial resistance is to target QS proteins. In this study, a combined multi-level computational approach was applied to find possible inhibitors against P. aeruginosa QS regulator protein MvfR, also known as PqsR, using a database of approved FDA drugs, as a repurposing strategy. Fifteen compounds were identified as highly promising putative MvfR inhibitors. On those 15 MvfR ligand complexes, molecular dynamic simulations and MM/GBSA free-energy calculations were performed to confirm the docking predictions and elucidate on the mode of interaction. Ultimately, the five compounds that presented better binding free energies of association than the reference molecules (a known antagonist, M64 and a natural inducer, 2-nonyl-4-hydroxyquinoline) were highlighted as very promising MvfR inhibitors. View Full-Text
Keywords: drug repurposing; Pseudomonas aeruginosa; computer-aided drug design (CADD); biofilms; quorum sensing drug repurposing; Pseudomonas aeruginosa; computer-aided drug design (CADD); biofilms; quorum sensing
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MDPI and ACS Style

Vieira, T.F.; Magalhães, R.P.; Simões, M.; Sousa, S.F. Drug Repurposing Targeting Pseudomonas aeruginosa MvfR Using Docking, Virtual Screening, Molecular Dynamics, and Free-Energy Calculations. Antibiotics 2022, 11, 185. https://doi.org/10.3390/antibiotics11020185

AMA Style

Vieira TF, Magalhães RP, Simões M, Sousa SF. Drug Repurposing Targeting Pseudomonas aeruginosa MvfR Using Docking, Virtual Screening, Molecular Dynamics, and Free-Energy Calculations. Antibiotics. 2022; 11(2):185. https://doi.org/10.3390/antibiotics11020185

Chicago/Turabian Style

Vieira, Tatiana F., Rita P. Magalhães, Manuel Simões, and Sérgio F. Sousa. 2022. "Drug Repurposing Targeting Pseudomonas aeruginosa MvfR Using Docking, Virtual Screening, Molecular Dynamics, and Free-Energy Calculations" Antibiotics 11, no. 2: 185. https://doi.org/10.3390/antibiotics11020185

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