Fig. 5.

Molecular binding of triglycerides (TG) with Toll-like receptors (TLR2/1 and TLR2/6). (A) The images demonstrate the positions of TG molecules and TLRs at the start (after docking) and the end (after 300 ns of molecular dynamics [MD] simulation). Docking predicts how a small molecule (like TG) might fit into a specific site on a protein. MD simulation models the movements and interactions of atoms over time, allowing us to observe how TG and the TLRs interact and change shape. Enlarged views show fatty acid chains of TG penetrating the main binding site of TLR2 and TLR1 and interacting with key residues to stabilize TLR2/1 heterodimer. In contrast, for the TLR2/6 complex, the fatty acids primarily interact with the main binding site of TLR2, but not with TLR6 without stabilizing the TLR2/6 heterodimer. TLR2, TLR1, and TLR6 are shown in green, magenta, and orange, respectively. TG is represented in stick form. The structures for TLR2/1-PAM3 and TLR2/6-PAM2 (positive control forms) are not shown here. (B) The graph shows the distance between the center of mass (COM) of TG, PAM3, and PAM2 and the primary TLR binding sites over time. The COM represents the average position of the mass of each molecule. Measuring its distance to the binding site of TLRs helps track how TG moves into the binding pocket and supports dimer stabilization by remaining bound to the receptors.