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Molecular docking and dynamics studies on novel benzene sulfonamide substituted pyrazole-pyrazoline analogues as potent inhibitors of Plasmodium falciparum Histo aspartic protease
M. Thillainayagam, ,
Published in Taylor and Francis Ltd.
PMID: 31411122
Volume: 38
Issue: 11
Pages: 3235 - 3245

Malaria is the major health issue in African, Asian and Mediterranean regions of the world. Due to the emerging resistance by the parasites and mosquitoes for the current medications and insecticides, respectively, the malaria free human world can be attained only by the novel design and development of new anti-malarial drugs. Hence, we attempted to carry out in silico screening of benzene sulfonamide substituted pyrazole-pyrazoline series against Histo aspartic protease. Our results reveal that the 65% of the data set with the free binding energy in the range of –11.58 to –11.21 kcal/mol, which is categorized as ‘high scoring’. Ligands are docked with the catalytic residues Asp 215, Ser 75, Thr 33 and Ala 217, respectively. Molecular dynamic simulation study of free enzyme and the enzyme complex with 4-(5-(4-methoxyphenyl)-1’phenyl-3’-(p-tolyl)-3,4-1’H,2H-[3,4’-bipyrazol]-2-yl)benezenesulfonamide indicated structural stability. The trajectory analysis of complex reveals that the HAP–ligand complex is more stable than the free HAP. We are of the opinion that our results will be useful for designing potential anti-malarial compounds. AbbreviationsADT auto dock toolsBSPP benzene sulfonamide substituted pyrazole-pyrazolineCQ chloroquineHAP histo aspartic proteaseK KelvinMD molecular dockingMM/PBSA molecular mechanics/Poisson Boltzmann surface areaNVT normal volume and temperatureNPT normal pressure and temperatureNs nanosecondsPDB protein data bank.pdb program data base formatP. falciparumPlasmodium falciparumPs picosecondsPMs plasmepsinsP. vivaxPlasmodium vivaxRg radius of gyrationRMSD root mean square deviationRMSF root mean square fluctuationWHO World Health Organization Communicated by Ramaswamy H. Sarma. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

About the journal
JournalData powered by TypesetJournal of Biomolecular Structure and Dynamics
PublisherData powered by TypesetTaylor and Francis Ltd.