Abstract:
Despite advancement in malaria research, it continues to be a global problem. Of the estimated
655,000 malaria deaths occurring 2011, about 90% occurred in Africa and mainly in children under
the age of 5 years. The current WHO first-line treatment for malaria is the artemisinin based
combination therapies (ACTs). With increased reports of reduced susceptibility of Plasmodium
falciparum to ACTs, the search for new drugs is vital. The aim of this study was to screen
Plasmodium falciparum genome for possible drug targets and model novel drug compounds by use
of bioinformatics approaches. Plasmodium falciparum genome sequence data was downloaded and
screened using GenScanTM for potential drug targets. Target sequences were validated using
sequence motif database ScanProsite for identification of specific residues likely to be involved in
function. The uniqueness of the target proteins was underpinned by use of homology search
algorithms specifically BLASTp. Some of the target proteins identified included glutathione reductase
(E.C 1.8.1.7), Enoyl Acyl Carrier Protein reductase (E.C 1.3.1.9). The 3D structures of the target
proteins were retrieved from PDB (RCSB Protein Data Bankhttp://
www.rcsb.org/pdb/home/home.do) and viewed using RasMol program to identify the active
sites. Docking and lead optimization was done using Arguslab software and lead molecules
generated. The drug relevant properties of the lead molecules were predicted using OSIRIS property
explorer. cDNA synthesis was done to determine the expression of the target genes.
