Please use this identifier to cite or link to this item:
Title: Computational insights into factor affecting the potency of diaryl sulfone analogs as Escherichia coli dihydropteroate synthase inhibitors
Authors: Das, B.K.
PV, P.
Chakraborty, D.
Issue Date: 2019
Citation: Computational Biology and Chemistry, 2019, Vol.78, , pp.37-52
Abstract: Dihydropteroate synthase (DHPS) is an alluring target for designing novel drug candidates to prevent infections caused by pathogenic Escherichia coli strains. Diaryl Sulfone (SO) compounds are found to inhibit DHPS competitively with respect to the substrate pABA (p-aminobenzoate). The extra aromatic ring of diaryl sulfone compounds found to stabilize them in highly flexible pABA binding loops. In this present study, a statistically significant 3D-QSAR model was developed using a data set of diaryl sulfone compounds. The favourable and unfavourable contributions of substitutions in sulfone compounds were illustrated by contour plot obtained from the developed 3D-QSAR model. Molecular docking calculations were performed to investigate the putative binding mode of diaryl sulfone compounds at the catalytic pocket. DFT calculations were carried out using SCF approach, B3LYP- 6-31 G (d) basis set to compute the HOMO, LUMO energies and their respective location at pABA binding pocket. Further, the developed model was validated by FEP (Free Energy Perturbation) calculations. The calculated relative free energy of binding between the highly potent and less potent sulfone compound was found to be ?3.78 kcal/ mol which is comparable to the experimental value of ?5.85 kcal/mol. A 10 ns molecular dynamics simulation of inhibitor and DHPS confirmed its stability at pABA catalytic site. Outcomes of the present work provide deeper insight in designing novel drug candidates for pathogenic Escherichia coli strains. 2018 Elsevier Ltd
Appears in Collections:1. Journal Articles

Files in This Item:
File Description SizeFormat 
5 Computational insights into factor.pdf3.97 MBAdobe PDFThumbnail

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.