Molecular modeling, simulation and virtual screening of MurD ligase protein from Salmonella typhimurium LT2

Samal, Himanshu Bhusan; Das, Jugal Kishore; Mahapatra, Rajani Kanta; Suar, Mrutyunjay

doi:10.1016/j.vascn.2015.03.005

Cited by 12 publications

(1 citation statement)

References 32 publications

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“…Homology modeling of P. aeruginosa DHODase was performed using MODELLER 9v12 59 . P. aeruginosa DHODase sequence (Accession ID: KGB88094) was retrieved from Uniprot database.…”

Section: Methodsmentioning

confidence: 99%

Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa

Guo

Wei

Xia

et al. 2016

Sci Rep

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The rising antibiotic resistance of bacteria imposes a severe threat on human health. Inhibition of bacterial virulence is an alternative approach to develop new antimicrobials. Molecules targeting antibiotic resistant enzymes have been used in combination with cognate antibiotics. It might be ideal that a molecule can simultaneously suppress virulence factors and antibiotic resistance. Here we combined genetic and computer-aided inhibitor screening to search for such molecules against the bacterial pathogen Pseudomonas aeruginosa. To identify target proteins that control both virulence and antibiotic resistance, we screened for mutants with defective cytotoxicity and biofilm formation from 93 transposon insertion mutants previously reported with increased antibiotic susceptibility. A pyrD mutant displayed defects in cytotoxicity, biofilm formation, quorum sensing and virulence in an acute mouse pneumonia model. Next, we employed a computer-aided screening to identify potential inhibitors of the PyrD protein, a dihydroorotate dehydrogenase (DHODase) involved in pyrimidine biosynthesis. One of the predicted inhibitors was able to suppress the enzymatic activity of PyrD as well as bacterial cytotoxicity, biofilm formation and antibiotic resistance. A single administration of the compound reduced the bacterial colonization in the acute mouse pneumonia model. Therefore, we have developed a strategy to identify novel treatment targets and antimicrobial molecules.

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“…Homology modeling of P. aeruginosa DHODase was performed using MODELLER 9v12 59 . P. aeruginosa DHODase sequence (Accession ID: KGB88094) was retrieved from Uniprot database.…”

Section: Methodsmentioning

confidence: 99%

Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa

Guo

Wei

Xia

et al. 2016

Sci Rep

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Determinants of Adenosine A_2A Receptors‐Perfluoroalkyl Sulfonates Complex: Multi‐Spectroscopic and Molecular Dynamics Simulation Study

Huang

et al. 2021

ChemistrySelect

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In this study, we determined the binding characteristics of perfluoroalkyl sulfonates (PFSAs) to the adenosine A2A receptor (A2AR) using various spectroscopic methods and computer simulation technologies. UV‐absorption, fluorescence spectra, and three‐dimensional fluorescence spectra results revealed the changes in the micro‐environment of the secondary structure of A2AR. By comparing the fluorescence spectroscopy of A2AR in the absence and presence of PFSAs, we found that PFSAs induced the static fluorescence quenching of A2AR. The thermodynamic parameters ▵H and ▵S indicated that van der Waals forces and electrostatic interactions predominantly stabilized the pollutant‐protein system. A molecular dynamics (MD) simulation study of the A2AR and A2AR‐PFSAs complex shows that A2AR‐PFSAs are stable. This study describes the binding mechanism of PFSAs to A2AR, which is very helpful in improving our understanding of the effect of PFSAs on peripheral tissues and the central nervous system.

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MurD inhibitors as antibacterial agents: a review

Azam

Jupudi

2020

Chem. Pap.

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Molecular modeling, simulation and virtual screening of MurD ligase protein from Salmonella typhimurium LT2

Cited by 12 publications

References 32 publications

Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa

Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa

Determinants of Adenosine A_2A Receptors‐Perfluoroalkyl Sulfonates Complex: Multi‐Spectroscopic and Molecular Dynamics Simulation Study

MurD inhibitors as antibacterial agents: a review

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Molecular modeling, simulation and virtual screening of MurD ligase protein from Salmonella typhimurium LT2

Cited by 12 publications

References 32 publications

Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa

Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa

Determinants of Adenosine A2A Receptors‐Perfluoroalkyl Sulfonates Complex: Multi‐Spectroscopic and Molecular Dynamics Simulation Study

MurD inhibitors as antibacterial agents: a review

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Determinants of Adenosine A_2A Receptors‐Perfluoroalkyl Sulfonates Complex: Multi‐Spectroscopic and Molecular Dynamics Simulation Study