Virtual binding of terpenoids to mycolic acid cyclopropane synthase CMAA2 of Mycobacterium tuberculosis Autodock software

Date

11-2006

Degree

Bachelor of Science in Chemistry

College

College of Arts and Sciences (CAS)

Adviser/Committee Chair

Ernesto J Del Rosario

Abstract

RUBIANES, FRANCIS HENNEL C. University of the Philippines Los Banos. November 2006. Virtual Binding of Terpenoids to Mycolic Acid Cyclopropane Synthase CmaA2 of Mycobacterium tuberculosis Using AUTODOCK Software

Adviser: Dr. Ernesto J. del Rosario

AUTODOCK software was used in the molecular docking of fifty-one (51) Terpenoids to mycolic acid cyclopropane synthase CmaA2. The ligands were prepared using the HYPERCHEM and two optimizations were done using the AMBER and PM3 methods. The macromolecule was obtained from Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank. After using the AUTODOCK Software, Gibbs energy of binding (△Gbinding ), docking energy (Edocked), and the Root-Mean-Square Deviation (RMSD) values were obtained. Two control dockings were performed, validation of binding energy by docking benzene to T4 Lysozyme and validation of the binding site by docking DDDMAB to the crystal structure of mycolic acid cyclopropane synthase. Visual Molecular Dynamics (VMD) was used in analyzing the receptor-ligand interactions. It was found that the two most potent inhibitors were Lanostane and Ophiobolane, with △Gbinding equivalent to -9.60,0.07 kcal/mol and -10.02,0.03 kcal/mol respectively. The residues where Lanostane interacts in the binding site of CmaA2 are: TYR 280, TYR 300, TYR 130, GLU 148, HIS 23, HIS 149, ARG 219, SER 42, TRP 254, and GLY 217. On the other hand, residues where the Ophiobolane interacted in the binding site of CmaA2 are: CYS 284, ARG 219, TYR 24, HIS 149, GLY 145, TYR 41, TYR 247. TYR 280, ILE 186, THR 293, PHE 206. GLY 217, and TRP 254. Results are attributed to the high hydrophobicity of the ligands. Also both ligands are competitive in their inhibition based on the conformation of DDDMAB in mycolic acid cyclopropane s■,.nthase CmaA2.

Language

English

Location

UPLB Main Library Special Collections Section (USCS)

Call Number

Thesis

Document Type

Thesis

This document is currently not available here.

Share

COinS