title: Molecular docking and molecular dynamics study on SmHDAC1 to identify potential lead compounds against Schistosomiasis.
abstract: Schistosomiasis, a disease caused by helminth parasites of genus Schistosoma. Its treatment intensively depends on single drug, praziquantel which increases the risk of development of drug-resistant parasite. Inhibitors of human HDAC are profoundly reported as novel anti-cancer drugs and used as new anit-parasitic agents. Schistosoma monsoni class I HDACs are expressed in all stages of life cycle and indicating that this enzyme is most likely a major target for the designing specific inhibitors. In order to find novel target for the treatment of Schistosomiasis, three dimensional structure of SmHDAC1 was generated, using homology modelling. Features of the generated structure, was then deduced with respect to conformation of peptide backbone, local compatibility of the generated structure in terms of energy and molecular dynamics study. Considering these features of the generated structure, we selected all the class 1 inhibitors reported so far, which showed interactions with HDACs. Virtual screening was done using reported inhibitors (70) and using SmHDAC1 and HsHDAC1 as the targets. On the basis of binding affinity and IC50 value, 24th ligand was selected for the molecular docking purpose. In this study, out of all the reported inhibitors, 24th inhibitor (N,8-dihydroxy-8-(naphthalen-2-yl) octanamide zinc id- ZINC13474421) showed better binding with SmHDAC1 (-8.1 kcal/mol) as compared to HsHDAC1 (-6.4 kcal/mol) in terms of binding energy and supported by IC50 value. This paper throws light on the reliable model for further structure based drug designing, concerning SmHDAC1 of S. mansoni. Molecular docking studies highlighted advantages of comparative in silico interaction studies of SmHDAC1 and HsHDAC1. N,8-dihydroxy-8-(naphthalen-2-yl) octanamide can further use for the clinical trial.
authors: Center of Bioinformatics, Institute of Interdisciplinary Studies, Nehru Science Center, University of Allahabad, Allahabad, India, raghvendra1986singh@gmail.com.
authors: Raghvendra
authors: R
authors: Singh
authors: Paras Nath
authors: PN
authors: Pandey
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D055808:Drug Discovery / Q000379:methods; D015801:Helminth Proteins / Q000737:chemistry*; D056284:Histone Deacetylase 1 / Q000737:chemistry* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D012556:Schistosomicides / Q000737:chemistry*; D016415:Sequence Alignment
chemical_list: D015801:Helminth Proteins; D056572:Histone Deacetylase Inhibitors; D012556:Schistosomicides; D056284:Histone Deacetylase 1