Virtual binding of alkaloids and terpenoids to NS5 dengue virus mRNA 2'-O-methyltransferase domain using dock software

Date

4-2010

Degree

Bachelor of Science in Chemistry

College

College of Arts and Sciences (CAS)

Adviser/Committee Chair

Ernesto J Del Rosario

Co-adviser

Conrado P. Monterola

Committee Member

Jose Rene L. Micor

Abstract

Dengue virus is presently believed to be the most extensive arthropod-borne disease in the world. Molecular docking is one of the many methods in computational chemistry which plays a significant role for the rational design of drugs. In this study, molecular docking was used to investigate the potential inhibitory activities of 85 alkaloid and terpenoid compounds toward the 2'-0-methyltransferase domain of the NS5 Dengue virus using the Dock Software. Before docking, validation was done on the location of the binding sites by re-docking the original ligands RVP and SAM to NS5MTaseov. The docking method was validated using test sets that were downloaded from the UCSF website. The crystal structure used was 1ABE. The three-dimensional crystal structure of NS5 Dengue Virus mRNA 2'-0- methyltransferase domain (NS5MTaseov) was obtained from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB-PDB). The macromolecule and ligands were prepared and optimized using Hyperchem Professional and UCSF Chimera. Thirty nine alkaloids and forty six terpenoids were docked to NS5MTaseov using Dock software. For comparison of results with AutoDock, the rankings of both alkaloids and terpenoids from Dock were compared and plotted against the rankings from AutoDock. The computed energy values for the re-docking of RVP and SAM were -57.99 and -47.53, respectively. Rigid docking of IABE gave % difference RMSD and energy values of 6.4 % and 4.7 %, respectively. Molecular docking of the ligands gave negative docking energy values and revealed that all were potential competitive inhibitors of SAM. The compound which showed the lowest docked energy was beta-carotene with a docked energy value of -52.42. The results from the Dock Software were in accordance with the results from the AutoDock software. Both revealed that beta-carotene is the most potent inhibitor.

Language

English

Location

UPLB Main Library Special Collections Section (USCS)

Call Number

LG 993.5 2010 C4 M34

Document Type

Thesis

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