In this study, we aimed to cover this gap by investigating the unbinding pathways of one agonist and five antagonists of TLR8 using MD simulations and the τ-Random Acceleration Molecular Dynamics (τRAMD) . τRAMD retrieves ligand unbinding events and relative residence times for a group of ligands interacting with the same protein . All the TLR8 agonist and antagonists investigated occupy the uridine binding site (Figure ) and have crystal structures for the complex with TLR8 available (PDB ID: 3W3L, 5WYX, 6KYA, 6TY5, 7CRF & 7YTX ).