Computational studies on PLK1 delta gene in cancer diseases.

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. Polo-like kinases (Plks) are a family of conserved serine/threonine kinases involved in the regulation of cell cycle progression through G2 and mitosis. One of them being PLK1, it’s over expression leads to a variety of cancers. Plk1 delta, an uncharacterized protein sequence found in UniProt was studied and found to consist of the N-terminal portion of plk1gene. The 3D protein structure of PLK1 delta was modeled and then the predicted structure was validated. Molecular dynamics simulation was performed to find the stability of the protein. The modelled protein was docked to BI 2536, an inhibitor of Plk1 to obtain conformation of least binding energy. The interacting sites between the protein and inhibitor were also analyzed.

Exploring novel drug targets in fatty acid pathway of Plasmodium falciparum.

The malarial parasite Plasmodium falciparum infects humans and proliferates rapidly inside the host before its detection. The proliferation step requires a large amount of lipids for membrane synthesis. Thus fatty acid biosynthesis occurring in the apicoplast plays an important role in causing cerebral malaria. In this study, we explored and analyzed these pathways using stoichiometric matrix, elementary flux modes and robustness analysis. Based on the above analysis, the robustness of this pathway diminished as the result of virtual enzyme knock out indicating four key enzymes, 3-oxoacyl-ACP synthase, 3-oxoacyl-ACP synthase, 3-oxoacyl-ACP synthase and Glycerol-3-phosphate o-acyl transferase. Among the four, the first three are existing drug targets. Subsequently, we also found that a combinatorial double knock out of these enzymes predicts further reduction in overall pathway enzyme activity. Thus, we propose multi drug targeting as a better way to treat brain malaria.