Abstract:In this study，a computational simulation was conducted in order to investigate the structural characteristics of immunoactivity fragments of Dendrobium officinale polysaccharide（DOP）and the mechanism of interaction with Toll - like receptor 4（TLR4）. Based on hydrophobic analysis of the TLR4 binding pocket，DOP oligosaccharides were divided into hydrophobic fragment screening and hydrophilic fragment screening.Molecular docking and molecular dynamics simulation were employed to analyze the structural characteristics of the most powerful DOP fragments and their interaction mechanism with TLR4. The results unveiled a heptasaccharide DOP fragment with the strongest activity，exhibiting a binding mode similar to that of classical substrate lipopolysaccharide. The hydrophobic tetrasaccharide fragment was bound to the hydrophobic binding cavity，and the hydrophilic trisaccharide fragment was bound to the positively charged region. In conclusions，the potentially immunomodulatory DOP was composed of an acetyl-modified hydrophobic tetrasaccharide fragment and a non-acetylated hydrophilic trisaccharide fragment，which mainly interacts with TLR4 through hydrogen bonding and hydrophobic interaction.