title: Identification of potent inhibitors against snake venom metalloproteinase (SVMP) using molecular docking and molecular dynamics studies.
abstract: Snake venom metalloproteinase (SVMP) (Echis coloratus (Carpet viper) is a multifunctional enzyme that is involved in producing several symptoms that follow a snakebite, such as severe local hemorrhage, nervous system effects and tissue necrosis. Because the three-dimensional (3D) structure of SVMP is not known, models were constructed, and the best model was selected based on its stereo-chemical quality. The stability of the modeled protein was analyzed through molecular dynamics (MD) simulation studies. Structure-based virtual screening was performed, and 15 potential molecules with the highest binding energies were selected. Further analysis was carried out with induced fit docking, Prime/MM-GBSA (ΔGBind calculations), quantum-polarized ligand docking, and density functional theory calculations. Further, the stability of the lead molecules in the SVMP-active site was examined using MD simulation. The results showed that the selected lead molecules were highly stable in the active site of SVMP. Hence, these molecules could potentially be selective inhibitors of SVMP. These lead molecules can be experimentally validated, and their backbone structural scaffold could serve as building blocks in designing drug-like molecules for snake antivenom.
authors.affiliation: a Department of Bioinformatics , Alagappa University , Karaikudi , Tamil Nadu 630004 , India.
authors.forename: Sathishkumar
authors.initials: S
authors.lastname: Chinnasamy
authors.forename: Selvakkumar
authors.initials: S
authors.lastname: Chinnasamy
authors.forename: Selvaraman
authors.initials: S
authors.lastname: Nagamani
authors.forename: Karthikeyan
authors.initials: K
authors.lastname: Muthusamy
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D006860:Hydrogen Bonding; D008024:Ligands; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D015203:Reproducibility of Results; D016415:Sequence Alignment; D012910:Snake Venoms / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D008024:Ligands; D011480:Protease Inhibitors; D012910:Snake Venoms; D045726:Metalloproteases
keywords: Prime/MM–GBSA; QPLD and density functional theory; SVMP; induced fit docking; molecular dynamics simulation