Search

LF is a bioactive protein, derived from colostrum and milk that has been found to possess various immunomodulatory, iron chelating, and antimicrobial properties, especially in its apo-form. Recent studies have demonstrated the functionality of LF in attaching to the S proteins of SARS-CoV-2, thereby preventing it from interacting with the ACE-2 receptor. However, the molecular mechanism mediating the process is poorly understood. In this study, molecular docking and MD simulations coupled with free energy calculations were applied to elucidate the key interaction of apo-LF and its N-lobe and C-lobe derivative forms with the RBD of coronavirus S proteins. This has also been extended into evaluating the L452R mutant, which is associated with the delta variant of SARS-CoV-2. The results demonstrate the efficacy of the apo-LF C-lobe in binding to the RBD of both variants, primarily through electrostatic attractions between the acidic residues of the former and the basic residues of each RBD. Furthermore, due to the additional arginine in the L452R variant, the interaction between the C-lobe and the latter is stronger, resulting in a more favourable binding and tightly bound structure. The simulations highlight that the C-lobe, followed by full-length apo-LF can form a multimeric complex with the RBD of SARS-CoV-2, indicating their potential use as novel therapeutics, particularly the cleaved C-lobe of apo-LF to disrupt the S proteins from binding to the host ACE-2 receptor. Communicated by Ramaswamy H. Sarma.

Lactoferrin is a protein, primarily found in milk that has attracted the interest of the food industries due to its health properties. Nevertheless, the instability of lactoferrin has limited its commercial application. Recent studies have focused on encapsulation to enhance the stability of lactoferrin. However, the molecular insights underlying the changes of structural properties of lactoferrin and the interaction with protectants remain poorly understood. Computational approaches have proven useful in understanding the structural properties of molecules and the key binding with other constituents. In this review, comprehensive information on the structure and function of lactoferrin and the binding with various molecules for food purposes are reviewed, with a special emphasis on the use of molecular dynamics simulations. The results demonstrate the application of modeling and simulations to determine key residues of lactoferrin responsible for its stability and interactions with other biomolecular components under various conditions, which are also associated with its functional benefits. These have also been extended into the potential creation of enhanced lactoferrin for commercial purposes. This review provides valuable strategies in designing novel nutraceuticals for food science practitioners and those who have interests in acquiring familiarity with the application of computational modeling for food and health purposes.

Lactoferrin is a protein, primarily found in milk that has attracted the interest of the food industries due to its health properties. Nevertheless, the instability of lactoferrin has limited its commercial application. Recent studies have focused on encapsulation to enhance the stability of lactoferrin. However, the molecular insights underlying the changes of structural properties of lactoferrin and the interaction with protectants remain poorly understood. Computational approaches have proven useful in understanding the structural properties of molecules and the key binding with other constituents. In this review, comprehensive information on the structure and function of lactoferrin and the binding with various molecules for food purposes are reviewed, with a special emphasis on the use of molecular dynamics simulations. The results demonstrate the application of modeling and simulations to determine key residues of lactoferrin responsible for its stability and interactions with other biomolecular components under various conditions, which are also associated with its functional benefits. These have also been extended into the potential creation of enhanced lactoferrin for commercial purposes. This review provides valuable strategies in designing novel nutraceuticals for food science practitioners and those who have interests in acquiring familiarity with the application of computational modeling for food and health purposes.