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

Date

4-2009

Degree

Bachelor of Science in Chemistry

College

College of Arts and Sciences (CAS)

Adviser/Committee Chair

Ernesto J Del Rosario

Co-adviser

Jelynne P Tamayo

Committee Member

Mary Ann O Torio

Abstract

Dengue virus infects more than 2.5 billion people annually and treatment of 1 human infection urgently needs research on anti-viral drugs. Computer based evaluation ) of inhibitors of a key virial enzyme may provide drug candidates from the most potent inhibitors. The present paper deals with molecular docking o5.,1-elected alkaloids and terpenoids to NS5 Dengue Virus mRNA 2'-O-methyltransferase (NS5MTaseuv). Control docking was done before docking the chosen ligands to NS5MTaseov by validation of binding energy using T4 lysozyme which was downloaded from RCSB Protein Database with PDB code INI-IB. The ligand ethyl benzene was redocked to T4 lysozyme; the calculated free energy of binding is -5.77 ± 0.01 kcal/mol (literature value: -5.76kcal/mol). Second validation of the binding site was done by docking RVP and SAII to the crystal structure of NS5MTaseov. Both RVP and SAII have RMSD values lower than 1.2 A which is considered valid according to Zhou and Madura (2003). The ligands used were prepared using HyperChem Professional. They were optimized using the Amber and PM3 methods. And the enzyme was downloaded from www.rcsb.org with the PDB code 1R6A. The most potent inhibitor (competitive inhibition) identified was (Beta +-carotene for terpenoids and echinuline for alkaloids. They have Ed.. iittuivident,-.4cr -21.20 and - 18.44 kcal/mol, respectively. The residues which interact with 0, +-carotene are LYS 181, TI IR 215, GLU 217, GLY 148, GLU 149, SER 150, ASP 146, LYS 61, ARG 57, GLY 81. GLU 111, GLY 83, CYX 82, TIIR 104, LYS 105, GLY 106, ILE 147, SER 211, ARG 212, LEU 210, ARG 38, ASP 37, LYS 30, GLU 35, LYS 29 AND TI IR 39. While for echinuline, ASP 146, LYS 181, LYS 61, ARG 57, GLY 58, ILE 147, GLY 148, GLY 81, ARG 212, IIIR 215, GLU 217, SER 214, SER 150, GLU 149, SER 56, GLY 86, CYX 82, LEU 210 AND SER 211. All of these amino acid residues have distances of less than 4.5 A from the bound ligand indicating non-covalent interactions.

Language

English

Location

UPLB Main Library Special Collections Section (USCS)

Call Number

LG 993.5 2009 C4 L37

Document Type

Thesis

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