In silico Designing of Potential Drug Compounds against Plasmodium falciparum

Malaria is one of the most significant public health problems in the world today; with 97 countries having on-going transmission. Despite advancement in malaria research, the disease continues to be a global problem. This is attributed to inadequate knowledge of Plasmodium falciparum’s physiopathology. This study employed in-silico approaches to design structure based potential drug candidates against Plasmodium falciparum malaria. The drug candidates in this study target proteins involved in parasite pyrimidine biosynthesis, type II fatty acid biosynthesis and detoxification of reactive oxygen species. Protein sequences were retrieved from PlasmoDB and 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 PyMOL program to identify the active sites. Structure prediction was done for targets with no available PDB 3D structure using PSvs2 (http://ps2.life.nctu.edu.tw). Ligand screening was done in PubChem databases. Docking and lead optimization was done using Autodock vina and lead molecules generated. The binding affinity analysis showed three lead molecules belonging to cyclopentane-diols and anilines with better docking scores of -10.49 kcal/mol, -10.3 kcal/mol and -12.96 kcal/mol. These molecules can further be tested and validated for their in vitro and in vivo efficacies as antimalarial drugs.