Interfacing β-casein – Phenolic compound interactions via molecular dynamics simulations with diffusion kinetics in delivery vehicles

The effect that protein-bioactive interactions may have on diffusion kinetics in foods and nutraceuticals was investigated by examining the diffusion kinetics of phenolic compounds (ferulic acid and epicatechin) of varying size, in the presence and absence of bovine β-casein. In the presence of the protein, the diffusion rate for ferulic acid and epicatechin was shown to decrease from 2.76 × 10-11 and 1.33 × 10-11 to 8.51 × 10-12 and 1.00 × 10-12 m2/s, respectively. The magnitude of the decrease in diffusion rate appears to be governed by interaction strength, with pulling simulations and umbrella sampling determining binding energies of -4.6 and -6.7 kcal mol-1 for protein-ferulic acid and protein-epicatechin interactions. This outcome indicates that dissociation of the bioactive from the delivery matrix may be the rate limiting process for diffusion in low solid systems. This work offers valuable insights for the use of pulling/umbrella simulations in understanding the impact of interactions on diffusion in foods and nutraceuticals.