An immunoinformatic approach employing molecular docking and molecular dynamics simulation for evaluation of l-asparaginase produced by Bacillus velezensis

Abstract

l-Asparaginase is one of the most important treatments for acute lymphoblastic leukemia. In this study, l-asparaginase-producing bacteria were isolated from the effluent and soil of the Isfahan slaughterhouse using M9 specific medium. Isolates were identified by 16SrRNA phylogenetic analysis. The immune characteristics were predicted. Molecular docking was performed between l-asparaginase and l-asparagine substrate using AutoDock tools 4.2 and AutoDock Vina. Molecular dynamics simulation studies were fulfilled using GROMACS. Five l-asparaginase-producing bacteria isolated that belonging to Stenotrophomonas maltophilia, Chryseobacterium sp. Chryseobacterium indologenes, Bacillus velezensis and Bacillus safensis. Predictions showed B. velezensis has better immune characteristics than B. safensis. The binding energies of the docked complex were calculated to be −4.34 and −4.9 kcal/mol. Molecular docking confirmed the interaction of l-asparaginase with its substrate. It was observed that the residues Thr36, Tyr50, Ala47, Thr116, Asp117, Met142, Thr193 and Thr192 were fundamental in protein-ligand complexation. Also, RMSD, RMSF, Rg, DSSP, SASA and MM-PBSA analysis showed that when l-asparaginase is bound to l-asparagine, it did not lose stability, secondary structure and compactness. Slaughterhouse soils and effluents are a potential source of l-asparaginase-producing bacteria that probably can probably produce l-asparaginase with more favorable immune properties than commercial enzymes. Communicated by Ramaswamy H. Sarma