Molecular Simulation Of 1,2,3-triazole And Isoindolinone Derivatives With HIV-1 Protease

Isoindolone and 1,2,3-triazole are common and important N-heterocyclic systems with a variety of biological activities,which play an important role in the field of medicine.In this paper,the interaction between the two derivatives and HIV-1 protease was simulated and analyzed.For isoindolones,Chem Draw and Chem3 D were first used to draw the structures and have a rough optimization.Then Auto Dock software was used to conduct semi-flexible docking between the above molecules and HIV-1 protease.Choose the compounds with the highest affinity score for the next dynamics simulation（RMSD and hydrogen bonding parameters for ligand and receptor were analyzed）,the results showed that after the system reaches equilibrium,residues ILE 50,ASP 29 and ASP 30 have a recognition effect with isoindolinone compounds,so isoindole Dolinone compounds could be used as potential targeted drugs for the protein,Then,g＿mmpbsa software was used to calculate the binding energy of the trajectory files of the dynamics simulation.The main influencing factors of the binding energy（coulomb electrostatic interaction energy,van der Waals force can,polar and nonpolar solvation free energy solvation free energy）were analyzed.The results showed that the solvent hindered the binding between the isindolone and protein.At the same time,it was also found that the amino acid residue ILE 50 played an important role in the binding of the compound,which provided a theoretical basis for the subsequent medicinal analysis.Chem Draw and Chem3 D were used to draw and roughly optimize1,2,3-triazole compounds,Autodock software was used to conduct semi-flexible docking between the above moleculesand HIV-1 protease.By analyzing the screening results,and select the ligand with the highest affinity score for kinetic simulation,and analyze RMSD and hydrogen bond between the ligand and the receptor.The results showed that after a short period of rotation of the system,the 1,2,3-triazole group formed more hydrogen bonds with the GLY 48 residue and was bound to enter the equilibrium state immediately,these results indicated that GLY 48 residue was an important active site for this type of compound,and 1,2,3-triazole group had significant biological activity for this protein,suggesting that1,2,3-triazole might be a potential specific drug for HIV-1 protease.