Identification of novel natural inhibitor for NorM - a multidrug and toxic compound extrusion transporter - an insilico molecular modeling and simulation studies

Journal of Biomolecular Structure & Dynamics
Manish KesherwaniDevadasan Velmurugan

Abstract

The emergence of bacterial multidrug resistance is an increasing problem in treatment of infectious diseases. An important cause for the multidrug resistance of bacteria is the expression of multidrug efflux transporters. The multidrug and toxic compound extrusion (MATE) transporters are most recently recognized as unique efflux system for extrusion of antimicrobials and therapeutic drugs due to energy stored in either Na(+) or H(+) electrochemical gradient. In the present study, high throughput virtual screening of natural compound collections against NorM - a MATE transporter from Neisseria gonorrhea (NorM-NG) has been carried out followed by flexible docking. The molecular simulation in membrane environment has been performed for understanding the stability and binding energetic of top lead compounds. Results identified a compound from the Indian medicinal plant "Terminalia chebula" which has good binding free energy compared to substrates (rhodamine 6 g, ethidium) and more favorable interactions with the central cavity forming active site residues. The compound has restricted movement in TM7, TM8, and TM1, thus blocking the disruption of Na+ - coordination along with equilibrium state bias towards occlude state of NorM tran...Continue Reading

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Citations

May 19, 2017·Journal of Biomolecular Structure & Dynamics·Manish KesherwaniDevadasan Velmurugan
Mar 3, 2018·Journal of Biomolecular Structure & Dynamics·Seethalakshmi SakthivelChandrasekar Raman
Mar 21, 2018·Journal of Biomolecular Structure & Dynamics·Gurkamaljit KaurJagdeep Kaur
Apr 6, 2018·Journal of Biomolecular Structure & Dynamics·Yue ZhangChunhua Li
Mar 30, 2018·Journal of Biomolecular Structure & Dynamics·Gaurav Raj DwivediSantosh Kumar Srivastava
Jun 29, 2017·Journal of Biomolecular Structure & Dynamics·Mohammed A KhedrKatharigatta N Venugopala

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Methods Mentioned

BETA
X-ray
in silico methods
PCA

Software Mentioned

MMPBSA
CHARMM
ProDy
VMD
Ligprep
Trajelix
EUCB
NMWIZ
Glide
MEMBPLUGIN

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