Binding and dynamics of diferuloylmethane-pyrimidine with C-Met protein

Abstract

C-Met protein antagonism is a prominent target for suppressing tumour growth. This study fabricates a new diferuloylmethane analogue by forming a ring in the mid-ketonic group and investigates its anticancer potential. First, molecular contact with the active site amino acids of 5AY5 was analysed through binding energy calculation. The best binding pose was submitted to an MD simulation in SPC solvent model for the interaction stability prediction. Further, the stable molecule was subjected to DFTB module to confirm the chemical reactivity. The result of diferuloylmethane analogue interaction with C-Met protein illustrates that the binding affinity was found to be −9.032 kcal/mol and the binding free energy of −71.73 kcal/mol for the molecule diferuloylmethane pyrimidine moiety. It formed π-π stacked and H-bond interactions with the C-Met protein. A 100 ns simulation tracked the diferuloylmethane-pyrimidine stabilized within <0.5 Å and strong interactions with more than 25 amino acids. Among these, TYR1230 had a 54 % with additional π-π stacked interactions formed. Compared to a standard molecule, it was more stable and formed a greater interaction. DFT studies depicted that electrostatic, hydrogen bonding, and hydrophobic interactions enhance the molecule's binding potential. Orbital calculations revealed a gap of 2.5479 eV, and thermodynamic behaviour suggesting increased stability and reduced chemical reactivity. These computational findings indicated that the diferuloylmethane–pyrimidine derivative shows potential as a C-Met inhibitor in cancer therapy.