+44-7360-538437- Biomedical Research (2010) Volume 21, Issue 2
Insilico docking for validation of drug leads on Superoxide dismutase of Homo sapiens and Plasmodium falciparum
Superoxide dismutases (SODs) are metalloproteins which bring about dismutation of super-oxides and prevent biological damage of cellular components during oxidative stress. The malarial parasite plasmodium falciparum has a well developed defense system which in-cludes superoxide dismutase, to scavenge free radicals and combat oxidative stress during the erythrocytic stage of its life cycle. Alignment studies of the primary structure of plasmo-dium falciparum SOD (PfFe-SOD) have shown it to be structurally distinct from human cy-tosolic copper-zinc SOD1 (Cu-ZnSOD1). This feature makes it a potential target for ther-apy. A search for new targets as well as drugs is essential due to the phenomenon of drug re-sistance to chloroquine which is the drug of choice for treatment of malaria. A few potential inhibitors from the library of synthetic molecules have already been studied using recombi-nant PfFe-SOD by Soulere et al. Three of the fifteen effective lead molecules SP72, SP13 and SP59 show significant inhibition of recombinant PfFe-SOD. However, no attempt was made to investigate whether these lead molecules interact with the host Cu-ZnSOD1. In this study, the lead molecules showing significant inhibition were prepared using Marvin sketch. Cu-ZnSOD1 and PfFe-SOD was docked to these lead molecules and the energy values obtained. The results indicate almost equal affinity of the lead molecules to both, host and parasite, SOD. In conclusion, this study shows that compounds which are found to be quite effective inhibitors of recombinant enzyme in vitro need to be validated by alternate methods since, in the living system, compounds tend to deviate from their in vitro behavior in an unpredicted way. Computational tools such as insilico docking provide the scientist with an alternate base for validation of lead molecules.
Author(s): Vidya G. Bernhardt, Janita R. T. Pinto, Vinitha R. Pai