Design Peptide to Disrupt Proper Orientation of NS1 DENV Dimerization Studied by Molecular Dynamics Simulation Asep Iin Nur Indra, Ihsanawati, Rukman Hertadi, Reza Aditama
Institute Technology of Bandung
Abstract
The development of peptides for the treatment of dengue hemorrhagic fever has been widely reported to be more effective and less toxic compared to organic compound drugs. The target protein used as therapy is mostly non-structural proteins (NS) DENV because they have important role in the life-cycle of the virus. The NS1 protein, which is a multifunctional protein, has become the newest target for viral therapy recently due to its involvement in viral replication and pathogenesis. The active form of this protein is in dimeric and hexameric conformation. In this study, the inactivation of the NS1 protein will be carried out by interfering with the dimerization process of this protein. In order to prevent or change the orientation of NS1 dimerization, a peptide with a certain sequence will be designed. Interfacial interactions on the NS1 DENV protein dimer occur in the β--roll region (sequence 1-29) through ionic interactions in addition to hydrogen bonding and hydrophobic interactions. Docking results showed that the designed peptide with the sequence of nineteen amino acid was able to interact closely with the beta-roll region of the monomeric NS1 protein. The molecular dynamics simulation (MD) study showed that this binding can disorient the dimeric formation of NS1 protein, thereby preventing the formation of the functional form of dimeric NS1 proteins
