title: High-affinity selective inhibitor against phospholipase A2 (PLA2): a computational study.
abstract: Phospholipase A2 (PLA2) is the most abundant protein found in snake venom. PLA2 induces a variety of pharmacological effects such as neurotoxicity, myotoxicity and cardiotoxicity as well as anticoagulant, hemolytic, anti-platelet, hypertensive, hemorrhagic and edema inducing effects. In this study, the three dimensional structure of PLA2 of Naja sputatrix (Malayan spitting cobra) was modeled by I-TASSER, SWISS-MODEL, PRIME and MODELLER programs. The best model was selected based on overall stereo-chemical quality. Further, molecular dynamics simulation was performed to know the stability of the modeled protein using Gromacs software. Average structure was generated during the simulation period of 10 ns. High throughput virtual screening was employed through different databases (Asinex, Hit finder, Maybridge, TOSLab and ZINC databases) against PLA2. The top seven compounds were selected based on the docking score and free energy binding calculations. These compounds were analyzed by quantum polarized ligand docking, induced fit docking and density functional theory calculation. Furthermore, the stability of lead molecules in the active site of PLA2 was employed by MD simulation. The results show that selected lead molecules were highly stable in the active site of PLA2.
authors.affiliation: a Department of Bioinformatics , Alagappa University , Karaikudi , Tamil Nadu , India and.
authors.forename: Sathishkumar
authors.initials: S
authors.lastname: Chinnasamy
authors.affiliation: b Department of Microbiology , Faculty of Medicine, Misurata University , Misurata , Libya.
authors.forename: Selvakkumar
authors.initials: S
authors.lastname: Chinnasamy
authors.affiliation: a Department of Bioinformatics , Alagappa University , Karaikudi , Tamil Nadu , India and.
authors.forename: Karthikeyan
authors.initials: K
authors.lastname: Muthusamy
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D020134:Catalytic Domain; D019295:Computational Biology; D017815:Elapidae / Q000235:genetics; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D064801:Phospholipase A2 Inhibitors / Q000737:chemistry*; D054467:Phospholipases A2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D012910:Snake Venoms / Q000737:chemistry* / Q000235:genetics
chemical_list: D008024:Ligands; D064801:Phospholipase A2 Inhibitors; D012910:Snake Venoms; D054467:Phospholipases A2
keywords: IFD; MD simulation; PLA2; QPLD; molecular modeling