title: In-silico analysis of Sirt2 from Schistosoma mansoni: structures, conformations, and interactions with inhibitors.
abstract: Sirtuins are NAD+-dependent lysine deacetylases member of the class III HDAC family. These are demonstrated to be therapeutic targets in parasitic diseases like schistosomiasis. Observations suggested that sirtuin enzyme is necessary for the functionality of fe/male reproductive system, due to which SmSirt2 is treated as a potential therapeutic target. There are no structural and molecular features of SmSirt2 have been reported yet. In this study, homology modeling has been used to determine the three-dimensional features of the SmSITRT2. Further, structure validation has been performed by energy minimization and Ramachandran plot. Validated structures are further subjected to molecular docking and virtual screening to find the best lead molecules for downstream analysis. Ten lead molecules were selected while comparing virtual screening of hSirt2 and SmSirt2 both. These leads are further compared with AKG2 which is known inhibitor of hSirt2 (-8.8 kcal/mol). Out of selected 10 leads, four of them (ZINC23995485 (-9.5 kcal/mol), ZINC53298162 (-9.4 kcal/mol), ZINC70927268 (-10.0 kcal/mol), ZINC89878705 (-11.2 kcal/mol)) have shown better interaction with SmSirt2, in which ZINC89878705 (-11.2 kcal/mol) shows a more compact packing as compared to AKG2 and rest of ligands. These molecules could be further subject to in vitro study and model of SmSirt2 has been proposed for further structure-based drug design projects concerning sirtuins from Schistosoma mansoni.
authors.affiliation: a Center of Bioinformatic, IIDS, Nehru Science Center , University of Allahabad , Allahabad 211002 , India.
authors.forename: Raghvendra
authors.initials: R
authors.lastname: Singh
authors.affiliation: a Center of Bioinformatic, IIDS, Nehru Science Center , University of Allahabad , Allahabad 211002 , India.
authors.forename: Swadha
authors.initials: S
authors.lastname: Singh
authors.affiliation: b Department of Mathematics , University of Allahabad , Allahabad 211002 , India.
authors.forename: Paras Nath
authors.initials: PN
authors.lastname: Pandey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015801:Helminth Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D012550:Schistosoma mansoni; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D015801:Helminth Proteins; D008024:Ligands; D056565:Sirtuin 2
keywords: SmSirt2; homology modeling; molecular docking; schistosomiasis; virtual screening