The protocol used in our package, Binding modes of Ligands Using Enhanced Sampling (BLUES) is thus a symmetric sequence of perturbation and propagation events, starting and ending with perturbation. The perturbation typically consists "thermodynamic perturbation" -modifying the potential energy function to change interactions between the ligand and the protein. However, the central perturbation step in each NCMC cycle is an instantaneous perturbation of the ligand coordinates. These perturbation (thermodynamic or instantaneous) events are interspersed with propagation via Langevin dynamics.