Computational design of disulfide cyclic peptide as potential inhibitor of complex NS2B-NS3 dengue virus protease

Development of genomic and proteomic studies coupled with computational sciences could facilitate the discovery of various target proteins and potential inhibitor to be developed as drugs. Several researches by molecular docking method have been conducted to design disulfide cyclic peptide ligand as potential inhibitors for NS2B-NS3 protease (NS2B-NS3 pro) of dengue virus serotype DENV-2 in order to inhibit replication of dengue virus. This research studied and evaluated the interaction of ligands and the enzyme in the hydrate state using molecular dynamics simulations at two different temperatures. Simulations were performed using two disulfide cyclic peptide inhibitors KRK and RKR, along with one linear peptide Bz-Nle-K-R-R-H as standard ligand. The result shows that dynamic movement of three proposed ligand in hydrated state affects ligand interactions. RKR ligand has the best affinity with the enzyme than KRK and standard ligand. This is shown by the ligand interaction with enzyme active site which remains stable during the simulation. At the end of simulation 300 K, RKR formed a hydrogen bond with Asp75 and at the end of simulation 312 K, RKR also maintained hydrogen bond with Asp75.