Virtual binding of flavonoids to mycolic acid cyclopropane synthase CMAA1 of Mycobacterium tuberculosis using autodock software

Date

4-2007

Degree

Bachelor of Science in Chemistry

College

College of Arts and Sciences (CAS)

Adviser/Committee Chair

Jelynne P. Tamayo

Abstract

Molecular docking of flavonoids to Mycolic acid cyclopropane synthase CmaA1 was studied using AUTODOCK Software. The three-dimensional crystal structure of CmaA 1 was obtained from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB-PDB). The structures of the ligands were drawn using Hyperchem Software which was also used to optimize the structures under Molecular Mechanics (AMBER) and semi-empirical (PM3) methods. Two docking controls were performed to validate the method: (1) validation of energy calculation, and (2) validation of binding site. To validate the calculated energies, N-butyl benzene was docked to T4-Lysozyme and the calculated energies were compared with the literature value (AGdockmg= -6.7 kcal/mol). T-test showed no significant differences between calculated and literature values at 5% confidence level. For the validation of binding site, didecyldimethylammonium bromide (DDDMAB) was removed and redocked to the enzyme (CmaA1). Visual Molecular Display (VMD) was used to view and analyze the interactions involved in the macromolecule-ligand complex. The binding of 51 flavonoid ligands to CmaA 1 was studied. Glabranin gave the most negative value for docking energy (AGdmking= -12.30 kcal/mol). It also showed the most number of ligand-receptor interaction making it the most potent inhibitor among the docked flavonoids. The enzyme residues involved in binding are: TYR 16, TYR 33. SER 34. GLY 137, ALA 138, GLU 140, HIS 141. ILE 169, ILE 195, PHE 200, GLY 203, ARG 204, LEU 205, TYR 232,LEU 236 and TRP 239.

Language

English

Location

UPLB Main Library Special Collections Section (USCS)

Call Number

Thesis

Document Type

Thesis

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