Molecular dynamic simulation of complex NS2B-NS3 DENV2 protease with potential inhibitors of cyclic tripeptide

Abstract

The pathogenic dengue virus (DV) is a growing global threat for which there is no specific treatment\rand prevention. Several vaccines have been developed against the disease, but they only prevent the\rdisease and reduce the risk of death. Consequently, the antiviral drug becomes the most powerful\rtreatment to solve this problem. The virus possesses a two component NS2B-NS3 protease that cleaves\rviral precursor proteins, and therefore represents a target for the development of antiviral drugs. In\rmany researches, several models of peptides inhibitor were generated in complexes with the NS2B-NS3\rDENV2 protease by performing molecular docking. The goal of this research was to study the\rinteraction of ligands as inhibitors for protein (enzyme) in solvent explicit condition by performing\rmolecular dynamics simulation at 300 and 312 K. The simulations were performed on four disulfide\rcyclic tripeptide ligands (RGR, KRK, RRA and RKR) and two proline-proline based cyclic peptide\rligands (RKK and KKR) compared with linear peptide inhibitor Bz-Nle-K-R-R-H as standard ligand. The\rresults provide conformational changes of enzyme-inhibitor complex that is shown by root-meansquare\rdeviation (RMSD) values. These results show that dynamic behavior of the complex occurs in\rthe presence of solvent. The interaction between ligand and amino acid residue of enzyme changed\rduring simulation. By these parameters, RKR becomes the best ligand compared with others. The\rligand has hydrogen bond interaction with the residue of active side, and is stable during simulation at\rboth temperatures. In conclusion, RKR ligand is proposed as an antiviral drug by performing molecular\rdynamics simulation