Molecular docking studies using garlic metabolites - a peek into the apoptotic pathway

Abstract

The organosulfur compounds derived from Garlic employ cytotoxic effects via (ROS) reactive oxygen species production for signaling, by activating cysteine proteases and stress kinases for apoptosis in human cancerous cell. With the increase in mitochondrial membrane permeability due to stress, the intracellular free [Ca2+] level increases. Thus, the activation of caspase-4 alongwith the expression of calreticulin indicates the involvement of (ER) endoplasmic reticulum stress in the process of apoptosis. Down-regulation of some BIRC proteins and Bcl-2, activation of Caspase3, Caspase-9 and Calpain, mitochondrial release of cytochrome c and Smac into the cytosol and overexpression of Bax are the related events included in apoptosis. In this work, homology modeling approach was employed in order to develop structures for these proteins. Some protein structures were readily available in the PDB database. Expasy’s Prot-param server were used for functional and physico-chemical characterization of the protein. Chemsketch was used for drawing molecules and ligands. Babel is the software used to convert .mol files to .pdb files for docking. Autodock software was used to dock ligands with their respective proteins, Patchdock and Firedock was also used to determine Protein-Protein interaction. Docking was performed to evaluate the binding constants of the different interactions mediated by garlic in the apoptotic pathway.

Keywords

• Docking
• apoptosis
• apoptotic pathways
• Reactive oxygen species
• protein structures