Computational protocol: Exploration of Sitagliptin as a potential inhibitor for the M1 Alanine aminopeptidase enzyme in Plasmodium falciparum using computational docking

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Protocol publication

[…] The three dimensional structure of the M1 Alanine aminopeptidase (PDB ID = 3EBG) of Plasmodium falciparum was downloaded from the Protein Data Bank. The quality check of the structure is performed through WHAT IF server. The possible molecular interactions of the substrate with M1 alanine aminopeptidase was predicted by docking the known substrate with the enzyme M1 alanine aminopeptidase. Ala- β- naphthylamide (βNA) was used to assay aminopeptidase and to determine Michaelis constant (Km). In the present study, the km of the Enzyme with the substrate, DL – Alanine β Napthylamide Hydrochloride was found out in silico with the Docking server. The low molecular weight protease inhibitors were screened for their efficacy to inhibit the action of M1 alanine aminopeptidase. About 100 low molecular weight protease inhibitors were downloaded from DrugBank, PubChem and MEROPS.Docking server offers a web-based easy to use interface that handles all aspects of molecular docking from ligand and protein setup. The active site of the enzyme was defined in the server prior to docking. The knowledge about the active site was obtained from the structural data provided by Mc Gowan et al., 2009 []. The Docking server was used to further identify the inhibitors of the active site for M1 alanine aminopeptidase. Computational docking was carried out using DockingServer. Gasteiger partial charges were added to the ligand atoms. Non polar hydrogen atoms were merged, and rotatable bonds were defined. Docking calculations were carried out on the protein – ligand interaction models. Essential hydrogen atoms, Kollman united atom type charges, and salvation parameters were added with the aid of AutoDock tools []. Docking simulations were performed using the Lamarckian genetic algorithm (LGA) and the Solis & Wets local search method []. Initial position, orientation, and torsions of the ligand molecules were set randomly. All rotatable torsions were released during docking. Each docking experiment was derived from 10 different runs that were set to terminate after a maximum of 2,50,000 energy evaluations. The population size was set to 150. During the search, a translational step of 0.2 Å, and quaternion and torsion steps of 5 were applied and the docking were performed. […]

Pipeline specifications

Software tools DockingServer, AutoDock
Databases DrugBank
Application Protein interaction analysis
Organisms Plasmodium falciparum