Understanding the mechanism of amygdalin's multifunctional anti-cancer action using computational approach.

Amygdalin possesses anticancer properties and induces apoptosis. Based on experimental studies the presence of amygdalin with cancer cells led to activate the caspase-3 and BAX and inhibits Bcl-2 and Poly (ADP-ribose) polymerase-1 (PARP-1) but without deep information on action mode of these activities. Herein, we leaped forward to examine the molecular dynamics of the bound amygdalin and free ligand proteins, to identify precise action (conformation changes in targeted proteins) of amygdalin through using double docking and molecular dynamics (MD) simulations for 50 ns time scale. The MD simulations revealed that the binding of amygdalin led to disrupting the interaction between the Bcl-2/BAX complex. We furthermore conducted MD simulation for Bcl-2/amygdalin to investigate the stability of the complex which is responsible for inhibition of Bcl-2. It has been obtained a stable Bcl-2/amygdalin complex during the 50 ns. The results give a detail explanation of how amygdalin activates BAX and inhibits Bcl-2. For caspase-3, the matter is different, we found that amygdalin led to disrupting the interaction of caspase-3's two chains for intervals during 50 ns and then bind together repeatedly. The mechanism of caspase-3's activation through switching by disrupt the interacts for periodic intervals manner. For PARP-1, the dynamics simulations results indicated amygdalin interacts with PARP-1's binding site and forms stable interaction during simulation to render it inactive. Hence, amygdalin revealed a supernatural behavior through the MD simulations: it revealed a further clarification of the mystery amygdalin's experimental action which can act as a multifunctional drug in the cancer therapeutics.Communicated by Ramaswamy H. Sarma.