Virtual binding of flavonoids to mycolic acid cyclopropane synthase CMAA2 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

Ernesto J Del Rosario

Co-adviser

Dolores P. Buquirian

Committee Member

Jelynne P Tamayo

Abstract

The molecular docking of seventy (70) flavonoids to mycolic acid cyclopropane synthase CMaA2 was performed using the AUTODOCK Software. In order to prepare the ligands in docking, the HYPERCHEM program was used to draw and optimize the ligands using AMBER and PM3 methods. The macromolecule was obtained from Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank. In a successful docking between ligand and macromolecule, docking energies and the Root-Mean-Square (RMSD) values were obtained. Four control dockings were performed to validate the study. Specifically, three control dockings were done for the validation of the binding energy by docking camphane, norcamphor, and camphoroquinone in cythochrome p450cam. On the other hand, the validation of the binding site was done by docking DDDMAB to the crystal structure of mycolic acid cyclopropane synthase. Visual Molecular Dynamics (VMD) was used in analyzing the receptor-ligand interactions, and at the same time, make visual representations of the docked structure. For this study, the two most potent flavonoid inhibitors were Cyclomulberrin and Mulberrin, with Edockcd equivalent to -15.11 kcal/mol, and -12.49 kcal/mol, respectively. The main interactions between Cyclomulberrin and the binding site of CmaA2 were found to be: TYR 24, TYR 41, SER 42, GLY 145, GLU 148, HIS 149, ILE 184, ILE 207, ILE 210, LEU 211, PHE 215, GLY 217, GLY 218, ARG 219, LEU 220, TYR 247, LEU 251, TRP 254, TYR 280, CYS 284, LEU 287, PHE 288, and THR 293. For Mulberrin, on the other hand , the residues involved were TYR 24, TYR 41, GLY 145, GLU 148, HIS 149, ILE 184, ILE 207, ILE 210, LEU 211, PHE 215, GLY 218, ARG 219, LEU 220, TYR 247, LEU 251, TRP 254, TYR 280, CYS 284, LEU 287, PHE 288, and THR 293. All of the interactions were hydrophobic interactions (34.5 A). Both of these ligands were competitive inhibitors based mainly on the conformation of the DDDMAB in mycolic acid cyclopropane synthase. By comparing the results obtained in this study to that of Baja and Rubianes, it was illustrated that the binding energies of Flavonoids bound to CmaA2 are more negative than Alkaloids and Terpenoids, making it a better class of compounds to be further studied for the possible drug development against tuberculosis.

Language

English

Location

UPLB Main Library Special Collections Section (USCS)

Call Number

LG 993.5 2007 C4 L37

Document Type

Thesis

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