Virtual Screening of Novel Glucosamine-6-Phosphate Synthase Inhibitors
Authors: Lather Amit , Sharma Sunil , Khatkar Anurag 
Published: March 2018

Background:

Infections caused by microorganisms are the major cause of death today. The
tremendous and improper use of antimicrobial agents leads to antimicrobial resistance.

Aim and Objective:

Various currently available antimicrobial drugs are inadequate to control the infections and
lead to various adverse drug reactions. Efforts based on computer-aided drug design (CADD) can excavate a
large number of databases to generate new, potent hits and minimize the requirement of time as well as money
for the discovery of newer antimicrobials. Pharmaceutical sciences also have made development with advances in
drug designing concepts. The current research article focuses on the study of various G-6-P synthase inhibitors
from literature cited molecular database. Docking analysis was conducted and ADMET data of various molecules
was evaluated by Schrodinger Glide and PreADMET software, respectively. Here, the results presented efficacy
of various inhibitors towards enzyme G-6-P synthase. Docking scores, binding energy and ADMET data of
various molecules showed good inhibitory potential toward G-6-P synthase as compared to standard antibiotics.
This novel antimicrobial drug target G-6-P synthase has not so extensively been explored for its application in
antimicrobial therapy, so the work done so far proved highly essential. This article has helped the drug
researchers and scientists to intensively explore about this wonderful antimicrobial drug target.

Materials and Methods:

The Schrodinger, Inc. (New York, USA) software was utilized to carry out the
computational calculations and docking studies. The hardware configuration was Intel® core (TM) i5-4210U CPU
@ 2.40GHz, RAM memory 4.0 GB under 64-bit window operating system. The ADMET data was calculated by
using the PreADMET tool (PreADMET ver. 2.0). All the computational work was completed in the Laboratory
for Enzyme Inhibition Studies, Department of Pharmaceutical Sciences, M.D. University, Rohtak, INDIA.

Results:

Molecular docking studies were carried out to identify the binding affinities and interaction between the
inhibitors and the target proteins (G-6-P synthase) by using Glide software (Schrodinger Inc. U.S.A.-Maestro
version 10.2). Grid-based Ligand Docking with Energetic (Glide) is one of the most accurate docking softwares
available for ligand-protein, protein-protein binding studies. A library of hundreds of available ligands was
docked against targeted proteins G-6-P synthase having PDB ID 1moq. Results of docking are shown in Table 1
and Table 2. Results of G-6-P synthase docking showed that some compounds were found to have comparable
docking score and binding energy (kj/mol) as compared to standard antibiotics. Many of the ligands showed
hydrogen bond interaction, hydrophobic interactions, electrostatic interactions, ionic interactions and π- π
stacking with the various amino acid residues in the binding pockets of G-6-P synthase.

Conclusion:

The docking study estimated free energy of binding, binding pose andglide score and all these
parameters provide a promising tool for the discovery of new potent natural inhibitors of G-6-P synthase. These
G-6-P synthase inhibitors could further be used as antimicrobials. Here, a detailed binding analysis and new
insights of inhibitors from various classes of molecules were docked in binding cavity of G-6-P synthase. ADME
and toxicity prediction of these compounds will further accentuate us to study these compounds in vivo. This
information will possibly present further expansion of effective antimicrobials against several microbial
infections.