title: In silico screening of novel inhibitors of M17 Leucine Amino Peptidase (LAP) of Plasmodium vivax as therapeutic candidate.
abstract: M17 LAP (Leucine Amino Peptidase) plays an important role in the hydrolysis of amino acids essential for growth and development of Plasmodium vivax (Pv), the pathogen causing malaria. In this paper a homology model of PvLAP was generated using MODELLER v9.15. From different in-silico methods such as structure based, ligand based and de novo drug designing a total of 90 compounds were selected for docking studies. A final list of 10 compounds was prepared. The study reported the identification of 2-[(3-azaniumyl-2-hydroxy-4-phenylbutanoyl) amino]-4-methylpentanoate as the best inhibitor in terms of docking score and pharmacophoric features. The reliability of the binding mode of the inhibitor is confirmed by molecular dynamics (MD) simulation study with GROMACS software for a simulation time of 20ns in water environment. Finally, in silico ADMET analysis of the inhibitors using MedChem Designer v3 evaluated the drug likeness of the best hits to be considered for industrial pharmaceutical research.
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India.
authors.forename: Subhashree
authors.initials: S
authors.lastname: Rout
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar 751024, Odisha, India. Electronic address: rmahapatra@kiitbiotech.ac.in.
authors.forename: Rajani Kanta
authors.initials: RK
authors.lastname: Mahapatra
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D062126:Databases, Chemical; D004353:Drug Evaluation, Preclinical; D007931:Leucyl Aminopeptidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008024:Ligands; D062105:Molecular Docking Simulation; D010966:Plasmodium vivax / Q000187:drug effects / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015203:Reproducibility of Results; D020539:Sequence Analysis, Protein; D040681:Structural Homology, Protein
chemical_list: D000962:Antimalarials; D008024:Ligands; D011480:Protease Inhibitors; D015800:Protozoan Proteins; D007931:Leucyl Aminopeptidase
keywords: De novo drug design; M17LAP; Molecular docking; Molecular dynamics; Pharmacophore