Arli Aditya Parikesit - The Computation of Cyclic Peptide with Prolin-Prolin Bond as Fusion Inhibitor of DENV Envelope Protein through Molecular Docking and Molecular Dynamics Simulation

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      Publication Details (including relevant citation   information):

      Parikesit, Arli Aditya, Zahroh, Hilyatuz, Nugroho, Andreas S,   Hapsari, Amalia, Tambunan, Usman Sumo Friend., ICBS UGM   Conference Proceedings. 2013, pp 415-421

      Abstract:

      A disease that caused by dengue virus (DENV) has become the major   health problem of the world. Nowadays, no effective treatment is   available to overcome the disease due to the level of dengue   virus pathogeneses. A novel treatment method such as antiviral   drug is highly necessary for coping with the dengue disease.   Envelope protein is one of the non-structural proteins of DENV,   which engaged in the viral fusion process. It penetrates into the   host cell to transfer its genetic material into the targeted cell   followed by replication and establishment of new virus. Thus, the   envelope protein can be utilized as the antiviral inhibitor   target. The fusion process is mediated by the conformational   change in the protein structure from dimer to trimer state. The   previous research showed the existing cavity on the dimer   structure of the envelope protein. The existing ligand could get   into cavity of the envelope protein, stabilize the dimer   structure or hamper the transition of dimer protein into trimer.   In this fashion, the fusion process can be prevented. The aim of   this research is designing the cyclic peptide with prolin-prolin   bond as fusion inhibitor of DENV envelope protein through   molecular docking and molecular dynamics simulation. The   screening of 3,883 cyclic peptides, each of them connected by   prolin-prolin bond, through molecular docking resulted in five   best ligands. The pharmacological and toxicity character of these   five ligands were analised in silico. The result showed that   PYRRP was the best ligand. PAWRP was also chosen as the best   ligand because it showed good affinity with protein cavity.   Stability of ligand-protein complex was analyzed by molecular   dynamics simulation. The result showed that PYRRP ligand was able   to support the stability of DENV envelope protein dimer structure   at 310 K and 312 K. While PAWRP ligand actively formed complex   with the DENV envelope protein at 310 K compared to 312 K. Thus   the PYRRP ligand has a potential to be developed as DENV fusion   inhibitor.

      Address (URL): http://staff.ui.ac.id/system/files/users/aditya.parikesit/publication/published- icbs-proceeding-an.compressed.pdf