An Analysis of Lactodifucotetraose Using Molecular Docking and Dynamics Studies with Norovirus Capsid Protein

Abstract

A newborn’s “gold standard” nutritional supply is breastmilk, which provides primary energy since it contains oligosaccharides that resist enzyme hydrolysis within the upper digestive tract and are usually able to reach the colon. A key function of human milk oligosaccharides (HMOs) is to develop the immune system, prevent pathogenic infections, control the newborn gut microbiota, and function as prebiotics. Currently, Lactodifucotetraose (LDFT) HMO is simulated using molecular dynamics for 250 ns, and the prominent structural model is determined, with the data being deposited in the 3DSDSCAR database (www.3dsdscar.org). The LDFT models are docked with the Norovirus capsid protein, and the best docked model was simulated for 100-ns duration. Inter/intramolecular interactions enhance the LDFT complex structure’s stabilization and compact binding. Three binding modes were predicted using the binding free energy calculation. The complex structure deviation and fluctuation from the reference frame were analyzed. Overall analysis showed that the linear structure of LDFT can bind with NoVs in two modes. Hence, the binding efficacy of LDFT in two modes was effective due to its two fucose residues, which can bind as a hydrophobic cluster. The principal role of this LDFT HMO is to serve as an effective inhibitor of the Norovirus capsid protein.