Abstract: In this study, molecular docking combined with molecular dynamics (MD) simulations was employed to investigate the interaction mechanisms between phosphorylated triple-helical linear β-(1→3)-glucan (TH-CP) and Dectin-1. The results demonstrate that phosphorylation at the O6 and O4,6 positions introduce stable potential binding sites on the surface of Dectin-1, enabling TH-CP to form thermodynamically favorable and structurally stable complexes with the receptor. Among the three recognition modes identified at the potential binding site, complexes adopting an epitope recognition pattern exhibit a pronounced binding advantage. This behavior mainly arises from the cooperative interactions between TH-CP and a larger number of surrounding amino acid residues at the potential site, leading to enhanced van der Waals and electrostatic interactions. In addition, multiple hydroxyl groups within the phosphate moieties can act as flexible hydrogen bond donors and acceptors, giving rise to a novel hydrogen-bonding network distinct from that at the classical binding site. As a result, the recognition capability mediated by the potential binding site is comparable to that of unmodified β-(1→3)-glucan interacting with Dectin-1 at the classical binding site

Key words: β-(1→3)-Glucan, phosphorylated, Dendritic cell-associated C-type lectin-1, Recognition mode, Molecular dynamic simulation