Targeting Heat Shock Proteins 60 and 70 of Toxoplasma gondii as a Potential Drug Target: In Silico Approach

Heat shock proteins (Hsps) 60 and 70 are postulated as a potential drug target for toxoplasmosis due to its importance in the developmental and survival of Toxoplasma gondii ( T. gondii ). As of today, there have been no reports on three-dimensional (3D) structure of Hsp60 and Hsp70 deposited in the...

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Bibliographic Details
Published in:	Interdisciplinary sciences : computational life sciences Vol. 8; no. 4; pp. 374 - 387
Main Authors:	Ashwinder, Kaur, Kho, Mee Teck, Chee, Phui Mun, Lim, Wui Zhuan, Yap, Ivan K. S., Choi, Sy Bing, Yam, Wai Keat
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2016 Springer Nature B.V
Subjects:	Antiprotozoal Agents - pharmacology Antiprotozoal Agents - therapeutic use Binding sites Biomedical and Life Sciences Chaperonin 60 - metabolism Chemical bonds Chemical compounds Computational Biology/Bioinformatics Computational Science and Engineering Computer Appl. in Life Sciences Data banks Docking Drugs Free energy Health Sciences Heat shock proteins Homology Hsp60 protein HSP70 Heat-Shock Proteins - metabolism Hsp70 protein Hydrogen bonding Hydrophobicity Inhibitors Life Sciences Ligands Mathematical and Computational Physics Mathematical models Medicine Molecular Docking Simulation Original Research Article Proteins Protozoa Screening Searching Statistics for Life Sciences Theoretical Theoretical and Computational Chemistry Toxoplasma - drug effects Toxoplasma - metabolism Toxoplasma - pathogenicity Toxoplasma gondii Toxoplasmosis Toxoplasmosis - drug therapy Virtual screening Toxoplasmosis Molecular docking Heat shock protein Homology modeling
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Summary:	Heat shock proteins (Hsps) 60 and 70 are postulated as a potential drug target for toxoplasmosis due to its importance in the developmental and survival of Toxoplasma gondii ( T. gondii ). As of today, there have been no reports on three-dimensional (3D) structure of Hsp60 and Hsp70 deposited in the Brookhaven Protein Data Bank. Hence, this study was conducted to predict 3D structures for Hsp60 and Hsp70 in T. gondii by homology modeling. Selection of the best predicted model was done based on multiple scoring functions. In addition, virtual screening was performed to short-list chemical compounds from the National Cancer Institute (NCI) Diversity Set III in search of potential inhibitor against Hsp60 and Hsp70 in T. gondii. Prior to virtual screening, binding sites of Hsp60 and Hsp70 were predicted using various servers and were used as the center in docking studies. The Hsps were docked against known natural ligands to validate the method used in estimating free energy of binding (FEB) and possible interactions between ligand and protein. Virtual screening was performed with a total of 1560 compounds from the NCI Diversity Set III. The compounds were ranked subsequently according to their FEB. Molecular basis of interactions of the top five ranked compounds was investigated using Ligplot + . The major interactions exhibited were hydrogen bonding and hydrophobic interactions in binding to Hsp60 and Hsp70. The results obtained provided information and guidelines for the development of inhibitors for Hsp60 and Hsp70 in T. gondii .
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1913-2751 1867-1462
DOI:	10.1007/s12539-015-0107-x