Thermodynamic profile and molecular modeling of the interaction between Grb2 dimer and flavonoids Rutin and Morin

•Biophysical characterization of the interaction between Grb2 dimer and flavonoids Morin and Rutin;.•Fluorescence quenching shows that the interactions are entropically driven dominated by hydrophobic effects;.•Nuclear magnetic resonance provided the epitopes of the interaction guiding MD simulations and searching for the binding site;.•Grb2 is an important protein ubiquitously expressed inside the cell.•Grb2 is also a global regulator of FGFR2 kinase activity before extracellular stimulus;.•The equilibrium monomer-dimer of Grb2 works like a switch upon the regulation of the MAPK pathway.•Monomeric Grb2 up-regulates MAPK pathway while dimeric Grb2 would do the opposite.•The ability of mediating cell signaling transduction through its SH2 and SH3 domains makes Grb2 an important protein target to test the interaction with several molecules that present antitumor properties;.•Rutin and Morin competes for the same hydrophobic binding site located in the SH2 domain;.•SH2 domain is a worth valued macromolecule to test novel pharmacological compounds against cancer;.•These findings could level up Grb2 as an important target to test the interaction with polyphenols molecules already known to have anticancer properties;.•A study about how these phenolic molecules disturb the Grb2 mediating cell signaling are still missing;.•Dimeric Grb2 can be disrupted by interactions of small phosphopeptides interacting in the SH2 domain;.•There is no evidence that Morin and Rutin can promote Grb2 dimer dissociation during interaction;.•It still can be thought a situation where those molecules can possibly work somehow as a SH2 domain inhibitor and block the link for Ras/MAPK signaling transduction to prevent aberrant cell proliferation as well as cancer outcome.