In silico modelling of apo-lactoferrin under simulated gastric conditions: Structural dynamics, binding with β-lactoglobulin and α-lactalbumin, and functional implications

This study employs computational techniques to investigate whether the inclusion of beta-lactoglobulin and alpha-lactalbumin can enhance the molecular stability of apo-lactoferrin in conditions of gastric pH. Atomistic molecular dynamics simulations reveal that acidic pH results in weakened interactions between lactoferrin and the other proteins compared to those under neutral pH. Nevertheless, protein-protein dissociation free energy calculations using the umbrella sampling calculations confirm that some contacts are maintained between apolactoferrin and the other whey proteins, specifically the beta-lactoglobulin units. This is manifested as a broad energy minimum at the intermediate inter-molecular distance of the inter-protein free energy profiles; thereby, demonstrating the formation of a nano-scale flocculant, followed by a potential gel, composed of protein particles. Practically, this property could be exploited to entrap further bioactive components within the protein matrix for novel engineered food materials. Furthermore, it was found that the anti-bacterial peptide regions of apo-lactoferrin are unaffected by the acidic pH, indicating the potential capability of apo-lactoferrin to act against harmful bacteria. Overall, this work unveils an understanding at a molecular level regarding the structural changes of the aforementioned proteins that maybe beneficial for future advancement of nutraceuticals.

Automated summary

The study shows that acidic pH weakens interactions between lactoferrin and other proteins, but some contacts are maintained. This property could be used for developing novel food materials and indicates the potential antibacterial capability of apo-lactoferrin.