Showing 2 results for Molecular Dynamics Simulation
Zeinab Mollaie, Leila Karami, Elham Rezaee, Gilda Karimi,
Volume 10, Issue 3 (12-2023)
Abstract
It has been found that the second isoform of COX enzyme known as COX-2 plays an important role in inflammation and rheumatoid arthritis and osteoarthritis. Thus, designing COX-2 inhibitors to treat inflammation is among the most important goals of researchers. In this study, the inhibitory effect of 3 new imidazole derivatives on COX-2 was evaluated by in silico approach. Molecular docking was done using Autodock Vina and the best binding mode of inhibitors was used as input of molecular dynamics (MD) simulation. MD was performed using Gromacs software for 120 ns. Then, structural and thermodynamic analyzes (ΔGbinding) and prediction of physicochemical properties were performed. RMSD data showed the compounds reached a good equilibrium and had favorable stability during simulation. Also, the RMSF showed that due to binding of inhibitors, the fluctuations of complexes decreased and the active site residues had the lowest amount. Rg, SASA and DSSP analysis showed that the protein structure did not change significantly. It was also found that Ser530 and Tyr355 residues play a more effective role in hydrogen bond formation. Physicochemical parameters determined the good drug-likeness properties for all compounds. Structural and thermodynamic analyzes (MM-PBSA) and IC50 data indicate the favorable inhibitory effect of compound 5b.
Zahra Tavakoli, Behnaz Saffar, Karim Mahnam, Rohollah Hemmati,
Volume 11, Issue 3 (12-2024)
Abstract
One of the crises in the future for humanity is the epidemic of infectious diseases due to the antibiotic resistance of bacteria. Histatins family has antimicrobial activity against drug-resistant strains and wound healing properties. In this study, the first molecular dynamics simulation on Histatin 3 in the existence of water molecules and ions and also in the existence of Sodium Dodecyl Sulfate (SDS) micelle as a model of membrane bacteria was done separately via the GROMACS 5 package for 50 ns. Then, to increase antibacterial properties, eight mutations were designed and their structures were prepared. Then MD simulation was performed for each mutation with the same previous conditions and binding free energy via the MM/PBSA method of peptides with SDS micelle was calculated. Finally, 950 ns MD simulation in these conditions showed that the D1A-G9W mutation had the best binding free energy to the SDS micelle. Then this peptide and wild Histatin 3 peptide were synthesized, and antimicrobial properties were evaluated experimentally. The results of microbiological tests (MIC) indicated the value of this peptide, which is effective on gram-positive bacteria.
