
Threatening half of the world’s population Malaria still remains a serious public health problem in the developing world. Parasites of the genus Plasmodium cause the disease by degrading human hemoglobin as a source of amino acids for their growth and maturation. Plasmepsin II, an aspartic protease from the human intra erythrocytic parasite Plasmodium falciparum, is involved in degradation of the host cell haemoglobin within the acidic food vacuole of the parasite. Plasmepsin-II has become an attractive target for combating malaria through research regarding its importance in the P. falciparum metabolism and life cycle. In the present study, we have attempted with the help of virtual screening and molecular docking approach using Lamarckian Genetic Algorithm to elucidate the extent of specificity of Plasmepsin II towards different classes of Betulin. The docking result of the study of 534 molecules demonstrated that the binding energies were ranging from -10.06 kcal/mol to -6.00 kcal/mol, with the minimum binding energy of -10.06 kcal/mol. 8 molecules were showing hydrogen bonds with the catalytic amino acid residues of active site: Asp 34 and Asp 214. Further in-vitro and in-vivo study is required on these molecules as the binding mode provided hints for the future design of new derivatives with higher potency and specificity.