Before revision:  We employ the tau-Random Acceleration Molecular Dynamics (tauRAMD) method , in which a small randomly oriented force is applied to the ligand to facilitate its unbinding during MD simulations. We find that tauRAMD yields the ranking of dissociation rates for the simulated ligands, protein mutants and temperature conditions in good accordance with experiments . Comparison of the unbinding paths and metastable states of benzene from the L99A mutant reveals a good agreement of tauRAMD with much more computationally demanding conventional MD simulations.
After revision:  We employ the tau-Random Acceleration Molecular Dynamics (tauRAMD) method to a set of kinetically characterized complexes of T4 lysozyme mutants with engineered binding cavities. tauRAMD yields relative ligand dissociation rates in good accordance with experiments . Comparison of the unbinding paths and metastable states of benzene from the L99A mutant reveals a good agreement of tauRAMD with much more computationally demanding conventional MD simulations.