COMPUTER ASSISTED DRUG DESIGN (CADD) AGAINST PLASMODIUM FALCIPARUM

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.