Virtual binding of alkaloids and terpenoids to mycolic acid cyclopropane synthase CmaA2 of Mycobacterium tuberculosis 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

Request Access

To request access of this material, please email the administrator at uscs-mainlib.uplb@up.edu.ph

Abstract

Multi-drug resistance is observed in tuberculosis, which is a worldwide disease in humans caused by Mycobacterium tuberculosis. Anti-TB drug development has been facilitated by molecular drug design including docking of potential inhibitors to key enzymes in the causative organism. The present study deals with evaluation of potential inhibitors to M. tuberculosis mycolic acid cyclopropane synthase cmaA2. Twenty five alkaloids and 25 terpenoids were docked to cmaA2 using DOCK software. The three-dimensional crystal structure of cmaA2 was obtained from the Research Collaboratory for Structural Bioinformatics Protein Data Bank. Structures of ligands were drawn and optimized using HYPERCHEM software. Validation of energies was done by docking ornithine to periplasmic lysine-arginine-binding. Validation of the binding site was done by docking didecyldimethylammonium bromide (DDDMAB) to cmaA2. CHIMERA software was used to analyze the receptor-ligand interactions and make visual representations of docked structures.

All 50 ligands showed negative docking energies implying favorable enzyme- ligand binding; 35 ligands were found to be competitive inhibitors and bound to the primary binding site of cmaA2. Binding site residues were identified using Q-SITE FINDER as Y24, Y41, S42, L144, G145, E148, H149, I184, I207, I210, I211, F215, G218, R219, L220, Y247, L258, W254, Y280, C284, F288 and T293. Among the ligands docked to cmaA2, based on calculated docking energies and interactions with the binding site, alkaloid azatryptanthrin PAP505 and terpenoid protostane were the most potent inhibitors.

Language

English

Location

UPLB Main Library Special Collections Section (USCS)

Document Type

Thesis

This document is currently not available here.

Share

COinS