Computational design of de novo nutraceuticals: Effects of spray drying temperatures on the interaction between apo-lactoferrin whey protein complex and the peptidoglycan layer in lactic acid bacteria

Increasingly, lactic acid bacteria have been encapsulated into food formulations because of their health advantages, including modulation of the gut microflora. However, the molecular mechanism on how these bacteria interact with the encapsulating agent, which is typically composed of milk proteins is not fully comprehended. Accordingly, molecular dynamics simulations were employed to investigate the interaction between the cell wall component of these bacteria, specifically the peptidoglycan layer and a protein complex, comprising apo-lactoferrin, β-lactoglobulin, and α-lactalbumin at spray drying temperatures (68 and 110 °C). The results demonstrate that the peptidoglycan model interacts with the posterior N-lobe of apo-lactoferrin and the three-turn α-helix of β-lactoglobulin via van der Waals, electrostatic, and non-polar solvation interactions. Free energy calculations also show higher binding affinity at 110 °C than 68 °C, indicating that elevated temperatures are essential to facilitate hydrophobic interactions between the peptidoglycan component and the N-lobe of apo-lactoferrin. Furthermore, the secondary structure and the antibacterial regions in apo-lactoferrin are maintained following thermal simulations. The simulations not only highlight the formation of a stable complex, involving the peptidoglycan component, apo-lactoferrin, β-lactoglobulin, and α-lactalbumin, but also the preservation of the functionalities of apo-lactoferrin, which may provide valuable insights into the development of novel nutraceuticals.