Showing 2 results for Molecular Docking
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.
Dr. Reyhane Chamani, , , ,
Volume 11, Issue 4 (2-2025)
Abstract
Deactivation of drugs by enzymes, especially UDP-glucuronosyltransferases (UGT), is a reasons for resistance. The aim of this study was to investigate the interaction of UGT1A3, UGT1A1 and UGT2B7 enzymes with tyrosine kinase inhibitors. The structure of enzymes was made by homology modeling method and the structure of 300 tyrosine kinase inhibitors was obtained from Pubchem database. Molecular docking simulation was performed by PyRx 0.8 software and the complexes were sorted based on the most negative binding energy and zero RMSD and the amino acids involved in the binding were analyzed. In total, forty-five drugs were introduced as possible substrates of these three enzymes. The results showed that the binding site of these drugs were to the amino acids of the active site of the enzymes and the binding energy of the ligands to UGT1A1 was more negative than the other two enzymes. It can be suggested that the possible glucuronidation of these inhibitors by UGT enzymes can lead to two important events: first, their rapid removal from the blood circulation and creating drug resistance, and second, preventing bilirubin glucuronidation and increasing serum bilirubin level. Therefore, laboratory investigation of the relationship between these inhibitors and UGT enzymes can be necessary.
