Structure-based virtual screening, molecular docking, and molecular dynamics simulation approaches for identification of new potential inhibitors of class a ß-lactamase enzymes.

Bacteria are smart organisms that create drug resistance by decreasing the effect of antibiotics in different ways, such as secretion of the ß-lactamase enzymes. Finding the compounds that can act as the inhibitors of these enzymes is a great help in reducing drug resistance and treat all types of infections. In this study, using molecular docking and molecular dynamics simulation techniques, we introduced two Relebactam substructures as new inhibitors of class A ß-lactamase enzymes. Results of molecular docking show that the conformation of these two compounds in the active site of class A ß-lactamase enzymes has a good match with Relebactam and their binding affinity to enzymes is equal to or better than Relebactam. Results showed a good tendency for binding and the formation of van der Waals and hydrogen interactions between the desired compounds and the ß-lactamase enzymes. The results of the analysis of the molecular dynamics simulation trajectories showed that in the presence of the desired compounds, the second structures of the enzymes did not undergo many changes and in none of the systems, the binding of the compounds to the enzyme did not cause much instability, and in most cases made the structure stable. The hydrogen bonds were stable during the simulation time and in most cases, the new compounds formed more hydrogen bonds and had better binding affinity than Relebactam confirms the docking results. The results of this study can be helpful in designing new beta-lactamase inhibitors and new treatment methods to deal with drug resistance.Communicated by Ramaswamy H. Sarma.

In silico study of potential immunonutrient-based sports supplements against COVID-19 via targeting ACE2 inhibition using molecular docking and molecular dynamics simulations.

Use of some sports supplements can inhibit angiotensin-converting enzyme II (ACE2), a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as reviewed through molecular docking and sequent molecular dynamics (MD) simulations against this condition. The crystal structures of ACE2 receptors of SARS-CoV-2 and SARS-CoV, applied in docking analysis, were taken from the Protein Data Bank (PDB). The receptors were then prepared using the Molecular Operating Environment (MOE), as a drug-discovery software platform for docking. Supplements such as quercetin and beta glucan (ß-glucan) were the top docked compounds to ACE2 receptor though they strongly interacted with CoV target protein. The study data showed that immune responses to immunonutrient-based sports compounds (viz. quercetin and ß-glucan) in Coronavirus disease 2019 (COVID-19) were essential in mounting successful immune responses by athletes. While awaiting the development of an effective vaccine, there is a need to focus on immunonutrient-based sports supplements as preventive and therapeutic options that can be implemented in a safe and quick manner to bolster immune responses in athletes.Communicated by Ramaswamy H. Sarma.

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

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.