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 GenScanTMfor potential drug targets. Target sequences were validated using sequence motif database ScanProsite for identification of specific residues likely to be involved infunction. The uniqueness of the target proteins was underpinned by use of homology searchalgorithms 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 Bank-http://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.