Predicting non-covalent interactions between antioxidants in biological membranes through molecular dynamics

The synergistic association of different polyphenols has gained much interest in the food industry to develop efficient antioxidant cocktails, reducing the concentration of active agents and subsequently potential toxicity. The theoretical description and prediction of such processes are of central interest in this development. This study aims at benchmarking the performance of molecular dynamics (MD) to predict the formation of non-covalent complexes between π-conjugated antioxidants, including two prototypes (quercetin and vitamin E), in a pure 1,2-dipalmitoylphosphatidylcholine (DOPC) lipid bilayer. To reproduce the experimentally observed quenching of vitamin E fluorescence by quercetin, a sphere-of-action quenching model was applied. The predictive capability of MD simulations at capturing this non-covalent association was evaluated with five other π-conjugated potential partners of vitamin E, namely catechin, caffeic acid, myricetin, kaempferol, and galangin. The observed trend was consistent with experimental studies, validating the use of MD simulations as a tool to measure the potential synergism between natural antioxidants.