receptors. An important aspect would be to study the behaviour of diverse TLR agonists to determine if they display the same path preference and longer residence times observed here for the agonist of TLR8. The mechanistic insights provided here could be exploited to design antagonists with an unbinding pathway similar to the agonist, displaying longer residence times. A and B, PDB 7YTX: residues 438-460 for chains A and B). Residue 601 was missing in both 6KYA chains and residue 734 was missing in chain A, thus residues 599-601 were modelled in both chains and residues 733-735 were modelled in chain A due to the restriction of a minimum of three residues required for the Loop Modeller in MOE. Modeling of missing side chains and capping was performed using the Structure Preparation utility. The protein was protonated using the Protonate 3D function at pH 7 and temperature 300 K.