Molecular dynamics of interaction of Sesamin and related compounds with the cancer marker β-catenin: an in silico study.

By virtue of their regulatory role in the biological process, certain protein-protein complexes form potential targets for designing and discovery of drugs. Alteration set in the controlled formation of such complexes results in dysregulation of several metabolic processes, leading to diseased condition. β-catenin/Tcf4 complex is one such protein-protein complex found altered in colorectal epithelial cells resulting in activation of target genes leading to cancer. Recently, certain lignans from seeds of the oil crop sesame were found inhibiting initiation and progression of this type of cancer. Molecular mechanism involved in the process, however, is not yet known. By an in silico study, we present here a possible mechanism of interaction between the sesame lignans and β-catenin leading to inhibition of formation of the said complex, thereby elevating some of these ligands as potential lead molecules in the development of drugs for treatment of colon cancer. To achieve this objective, we performed docking, molecular dynamics simulation, and binding free energy analysis of target-ligand complexes. Using computational alanine scanning approach, the key pocket residues of β-catenin that interact with Tcf4 in the formation of complex were identified. The test molecules were initially evaluated for their drug-like properties by application of Lipinski's rule of five. Results of this study revealed that Sesamin, a furofuran lignan from sesame, has the highest affinity for β-catenin particularly with its residues that interact with Tcf4 and thus serving as a potential lead molecule for development of a drug for colon cancer.