After the NCMC move is accepted or rejected, velocities are randomized by drawing from the Maxwell-Boltzmann distribution appropriate for the temperature and then a phase of conventional MD is performed to better sample the other (protein/solvent) degrees of freedom. This full procedure consisting of NCMC moves plus MD steps is Figure : Lambda scaling over the course of our NCMC steps. The ligand's electrostatic interactions are first turned off, followed by the sterics, until the halfway point. The interactions are then turned on in reverse order. This protocol resembles what is typically done for efficient alchemical free energy calculations, such as binding free energy calculations. In particular, the electrostatics are the first to turn off and the last to turn on because having electrostatic interactions present without first turning off the steric interactions can lead to numerical instabilities. then repeated many times until convergence, and the populations can be then estimated from clustering the resulting trajectory and computing the time spent in each state.