The tauRAMD simulations were carried out using GROMACS-RAMD version 2.0 , the AMBER14SB force field and general Amber force field (GAFF) for protein and ligands, respectively. The ligand partial charges were calculated with quantum mechanical (QM) calculations using Gaussian 09 , Hartree-Fock 45 , and the 6-31G* basis set for all ligands except the neutral antagonist 6 of the crystal structure 7CRF , which contained an iodine. Due to the σ- hole of the iodine in ligand 6, and following previous work , we decided to use a higher basis set for QM calculations for ligand 6. For this ligand, the LANL2DZdp basis set was retrieved from the basis exchange server and applied. AmberTools 24 was used to generate the topology and coordinate files of the ligand.