Abstract\r\nToll-like receptors (TLRs) are pattern recognition receptors that recognize pathogens based on distinct molecular signatures.\r\nThe human (h)TLR1, 2, 6 and 10 belong to the hTLR1 subfamilies, which are localized in the extracellular regions and activated\r\nin response to diverse ligand molecules. Due to the unavailability of the hTLR10 crystal structure, the understanding of its\r\nhomo and heterodimerization with hTLR2 and hTLR1 and the ligand responsible for its activation is limited. To improve our\r\nunderstanding of the TLR10 receptor-ligand interaction, we used homology modeling to construct a three dimensional (3D)\r\nstructure of hTLR10 and refined the model through molecular dynamics (MD) simulations. We utilized the optimized structures\r\nfor the molecular docking in order to identify the potential site of interactions between the homo and heterodimer (hTLR10/2\r\nand hTLR10/1). The docked complexes were then used for interaction with ligands (Pam3CSK4 and PamCysPamSK4) using\r\nMOE-Dock and ASEDock. Our docking studies have shown the binding orientations of hTLR10 heterodimer to be similar with\r\nother TLR2 family members. However, the binding orientation of hTLR10 homodimer is different from the heterodimer due to\r\nthe presence of negative charged surfaces at the LRR11-14, thereby providing a specific cavity for ligand binding. Moreover,\r\nthe multiple protein-ligand docking approach revealed that Pam3CSK4 might be the ligand for the hTLR10/2 complex and\r\nPamCysPamSK4, a di-acylated peptide, might activate hTLR10/1 hetero and hTLR10 homodimer. Therefore, the current\r\nmodeled complexes can be a useful tool for further experimental studies on TLR biology.
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