In silico screening of natural products from specs database as inhibitors of fatty acid biosynthesis of Plasmodium falciparum using Fred and Autodock softwares

Date

4-2008

Degree

Bachelor of Science in Chemistry

College

College of Arts and Sciences (CAS)

Adviser/Committee Chair

Jelynne P Tamayo

Abstract

ABSTRACT

OCTAVIANO, JEFFREY B. College of Arts and Sciences, University of the Philippines Los Banos, April 2008. In Silica Screening of Natural products from SPECS database as inhibitors of Fatty Acid Biosynthesis of Plasmodium falciparum using FRED and AUTODOCK softwares.

ADVISER: Jelynne P. Tansayo

CONSULTANT: Dr. Ernesto J. del Rosario

Malaria which is caused by a protozoan parasite Plasmodium falciparum is one of the major infectious diseases in the world which continues to be a global health challenge. Computational chemistry provides an easier, less tedious and faster way of screening large sets of potential natural inhibitors that may be useful in drug design, prior to expensive and time consuming bioassay methods.

FRED software was used to screen 400 natural product compounds from SPECS database. AUTODOCK software was used in this study to determine the most suitable ligand that binds with Enoyl Acyl Carrier Protein Reductase (Fabl), P-Ketoacyl Acyl Carrier Protein Reductase (FabG), and 11-1-1ydroxyacyl Acyl Carrier Protein Dehydratase (FabZ) involved in the fatty acid biosynthesis of Plasmodium falciparum after the successful screening from 400 ligands to 40 lead ligands by FRED software. Enzymes and ligands were drawn and optimized using Hyperchem software. Residues involved in binding of enzyme-ligand complexes and the type of inhibition of each ligand were determined by using Visual Molecular Display (VMD).

One hundred twenty enzyme-ligand complexes (40 ligands per enzyme) were analyzed in the docking experiment. Among the docked inhibitors, Angelicin derivative (SPECS ID Number: AP-616/40879338) and 2-Benzyloxy-2',4'-dihydroxychalcone (SPECS ID Number: AK-087/42718376 ) were found to be the most potent inhibitors based on their binding energies. The two compounds which exhibited multiple inhibition, Angelicin derivative (AGbinding = -17.37 kcal/mol for Fabl, -20.142 kcal/mol for FabZ, -16.39 kcal/mol for FabG) and 2-Benzyloxy-2',4'-dihydroxyclialcone (AGbinding = -16.166 kcal/mol for FabI, -16.92 kcal/mol for FabZ, -15.95 kcal/mol for FabG) were found to be the most promising and had the highest values of free energy of binding; they also bound to the active site of more than one of the three enzymes (2-Benzyloxy-2',4'- dihydroxychalcone to Fabl, FabG and FabZ, Angelicin derivative to Fabl and FabZ).

Correlation between the rankings of FRED and AutoDock dockings for the three enzymes gave insignificant correlation. They are attributed to the difference in the scoring functions and the method of binding site specification used by the two programs.

Language

English

Location

UPLB Main Library Special Collections Section (USCS)

Call Number

LG 993.5 2008 C4 O28

Document Type

Thesis

This document is currently not available here.

Share

COinS