Evaluation of potential drugs against leishmaniasis targeting catalytic subunit of Leishmania donovani nuclear DNA primase using ligand based virtual screening, docking and molecular dynamics approaches.

Journal of Biomolecular Structure & Dynamics
Deep BhowmikDiwakar Kumar

Abstract

Leishmania donovani, causes leishmaniasis, a global health trouble with around 89 different countries and its population under its risk. Replication initiation events have been instrumental in regulating the DNA duplication and as the small subunit of L. donovani nuclear DNA primase (Ld-PriS) inherits the catalytic site, it plays a vital role in DNA replication. In this study we have aimed Ld-PriS for the first time as a prospective target for the application of drug against Leishmania parasite. 3-D structures of Ld-PriS were built and ligand-based virtual screening was performed using hybrid similarity recognition techniques. Ligands from the ZINC database were used for the screening purposes based on known DNA primase inhibitor Sphingosine as a query. Top 150 ligands were taken into consideration for molecular docking against the query protein (Ld-PriS) using PyRx and iGEMDOCK softwares. Top five compounds with the best docking score were selected for pharmacokinetic investigation and molecular dynamic simulation. These top five screened inhibitors showed very poor binding affinity toward the catalytic subunit of human primase indicating their safety toward the host normal replication mechanism. The top five compounds showed ...Continue Reading

References

Feb 1, 1995·Protein Engineering·A C WallaceJ M Thornton
Feb 24, 1995·The Journal of Biological Chemistry·W C Copeland, X Tan
Sep 1, 1993·Protein Science : a Publication of the Protein Society·C Colovos, T O Yeates
Nov 1, 1995·Proteins·A SaliM Karplus
May 1, 1997·Biochemistry and Molecular Biology International·K Tamiya-KoizumiS Yoshida
Jan 1, 1997·Methods in Enzymology·D EisenbergJ U Bowie
Apr 4, 1998·Antimicrobial Agents and Chemotherapy·N MbongoM Robert-Gero
Jul 13, 2000·Journal of Medicinal Chemistry·F Yoshida, J G Topliss
Oct 29, 2000·Journal of Medicinal Chemistry·W J EganJ J Baldwin
Nov 21, 2000·Trends in Biochemical Sciences·B Arezi, R D Kuchta
Feb 1, 2002·International Microbiology : the Official Journal of the Spanish Society for Microbiology·J M Pérez-VictoriaS Castanys
May 31, 2002·Journal of Medicinal Chemistry·Daniel F VeberKenneth D Kopple
Mar 30, 2004·Proteins·Jinn-Moon Yang, Chun-Chen Chen
Apr 29, 2005·Journal of Medicinal Chemistry·Yvonne C Martin
Oct 8, 2005·Journal of Computational Chemistry·David Van Der SpoelHerman J C Berendsen
Oct 28, 2005·Antimicrobial Agents and Chemotherapy·Saskia DecuypereJean-Claude Dujardin
Nov 1, 2005·Lancet·Henry W MurrayNancy G Saravia
Jul 18, 2006·Trends in Parasitology·Shaden Kamhawi
Jul 18, 2006·Nucleic Acids Research·Jian YeThomas L Madden
Dec 29, 2006·Protein Science : a Publication of the Protein Society·Saikat Chakrabarti, Christopher J Lanczycki
Mar 14, 2007·Bioorganic & Medicinal Chemistry Letters·Atul AgarwalMichael J Pucci
May 23, 2007·Nucleic Acids Research·Markus Wiederstein, Manfred J Sippl
Feb 1, 2008·Journal of Medicinal Chemistry·M Paul Gleeson
Nov 6, 2009·Journal of Biomedicine & Biotechnology·Helena C Maltezou
Jul 14, 2010·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Urbà GonzálezJorge Alvar
Nov 6, 2010·Journal of Computer-aided Molecular Design·Markus A Lill, Matthew L Danielson
Nov 16, 2010·Journal of Molecular Graphics & Modelling·Stuart W PaineKamaldeep K Chohan
Apr 29, 2011·Journal of Parasitic Diseases : Official Organ of the Indian Society for Parasitology·Bhavna Chawla, Rentala Madhubala
Oct 13, 2011·Molecular Systems Biology·Fabian SieversDesmond G Higgins
Nov 26, 2011·Nucleic Acids Research·Flora J Logan-KlumplerMatthew Berriman
May 12, 2012·Asian Pacific Journal of Tropical Medicine·Nisha SinghRakesh Kumar Singh
Jan 10, 2013·PLoS Pathogens·Laura-Isobel McCallGreg Matlashewski
Sep 6, 2013·Biochemistry·Tapan BiswasOleg V Tsodikov
Sep 12, 2013·Drug Target Insights·Md Lutful Amin
Jan 1, 2014·Antimicrobial Agents and Chemotherapy·Aneta KuronJaroslaw Dziadek
Jun 6, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Kai Hsin LiaoCalvin Yu-Chian Chen
Dec 1, 2004·Drug Discovery Today. Technologies·Christopher A Lipinski
Jul 22, 2014·Environmental and Molecular Mutagenesis·Luoping ZhangSundaresan Venkatactahalam
Jan 1, 2015·The Journal of Biological Chemistry·Andrey G BaranovskiyTahir H Tahirov
Jan 15, 2015·Journal of Clinical and Diagnostic Research : JCDR·Makesh Raj L SShankar K A

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Methods Mentioned

BETA
protein folding
X-ray
NMR

Software Mentioned

COACH
HybridSim
FAF
PyRx
BLAST
PROTOX
Pymol Molecular Visualization
Molsoft
ProSA
Automated Topology Builder ( ATB

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