title: Targeting Heat Shock Proteins 60 and 70 of Toxoplasma gondii as a Potential Drug Target: In Silico Approach.
abstract: 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.
authors: School of Health Sciences, International Medical University, 126 Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
authors: Kaur
authors: K
authors: Ashwinder
authors: School of Health Sciences, International Medical University, 126 Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
authors: Mee Teck
authors: MT
authors: Kho
authors: School of Health Sciences, International Medical University, 126 Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
authors: Phui Mun
authors: PM
authors: Chee
authors: School of Health Sciences, International Medical University, 126 Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
authors: Wui Zhuan
authors: WZ
authors: Lim
authors: Life Sciences Department, School of Pharmacy, International Medical University, 126 Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.
authors: Ivan K S
authors: IK
authors: Yap
authors: Natural Product and Drug Discovery Centre, Malaysian Institutes of Pharmaceuticals and Nutraceuticals, National Institutes of Biotechnology Malaysia, Ministry of Science, Technology and Innovation, Block 5-A, Halaman Bukit Gambir, 11700, Penang, Malaysia.
authors: Sy Bing
authors: SB
authors: Choi
authors: Life Sciences Department, School of Pharmacy, International Medical University, 126 Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia. waikeat_yam@imu.edu.my.
authors: Wai Keat
authors: WK
authors: Yam
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D018834:Chaperonin 60 / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D062105:Molecular Docking Simulation; D014122:Toxoplasma / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity*; D014123:Toxoplasmosis / Q000188:drug therapy*
chemical_list: D000981:Antiprotozoal Agents; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins
keywords: Heat shock protein; Homology modeling; Molecular docking; Toxoplasmosis; Virtual screening