Molecular dynamics modeling of different conformations of beta-glucan, molecular docking with dectin-1, and the effects on macrophages

This study investigated β-glucan with diverse conformations by using molecular dynamics simulations to analyze their conformational transitions in water. Stable conformations were docked with the Dectin-1 protein to evaluate key metrics such as favorable conformations, root-mean-square deviation, hydrogen bond interactions, and their effects on macrophage activity. Results revealed that single-chain β-1,3-glucan with a degree of polymerization (DP) of 24 forms aggregates in water, while triple-chain β-1,3-glucan with a DP of 6 tends to form double helices. Other models exhibited single-helical or entangled-helical structures, with β-1,3/1,4-glucans favoring compact triple helices. The β-1,3 glycosidic bond promotes compact helical structures, while the β-1,4 bond hinders folding, increasing rigidity. Branching via β-1,6 glycosidic bonds introduces flexibility and enhances hydrogen bonding with water, although longer branches may cause localized aggregation. Molecular docking suggests that Dectin-1's recognition sites are predominantly hydrophobic. Lower polymerization models improve binding affinity through structural complexity, whereas higher polymerization models enhance binding via helical characteristics and larger contact areas. The study provides a comprehensive perspective on Dectin-1's differential recognition of β-glucans.