Binding mechanism of caffeic acid and simvastatin to the integrin linked kinase for therapeutic implications: A comparative docking and MD simulation studies.

Integrin linked kinase (ILK) is a Ser/Thr kinase which regulates various integrin mediated signaling pathways, and is involved in cell adhesion, migration and differentiation. Alteration in the ILK is responsible for abnormal functioning of the cell system, which may lead to the cancer progression and metastasis. On the other hand, caffeic acid (CA) and simvastatin are used as antioxidants and possesses anticancer properties. Thus, inhibiting the kinase activity of ILK by CA and simvastatin may be implicated in the cancer therapy. In this study, we have performed molecular docking followed by 100 ns MD simulations to understand the interaction mechanism of ILK protein with the CA and simvastatin. Average potential energy was found to be highest in case of ILK-CA complex (-770949 kJ/mol). Binding free energy was found to be higher in case of simvastatin than CA. Our results indicate that simvastatin binds more effectively to the active pocket of ILK. We further performed MTT assay to understand its anticancer potential. Simvastatin shows the IC50 values for HepG2 and MCF-7 as 19.18 ± 0.12 µM and 13.84 ± 0.22 µM, respectively. However, the IC50 value of CA on HepG2 and MCF-7 were reported as 175.50 ± 1.44 µM and 144.90 ± 1.53 µM, respectively. Our study provides a deeper insights into the binding mechanism of simvastatin and CA to ILK which further opens a promising channel for their implications in cancer therapy.