Unless otherwise stated, for both the preliminary 50 ns log-spaced simulation and the 200 ns CEI-spaced simulation, the first 20 ns is discarded as an equilibration period, and potential energy time series data for each thermodynamic state is decorrelated using the pyMBAR timeseries module. Running on one NVIDIA ® Tesla ® V100 GPU, these combined 250 ns of REMD simulations (totaling 3 µs over all replicas) took approximately 8 hours to complete. In general, the energy decorrelation times for each thermodynamic state vary significantly, with states near the folding transition exhibiting slower decorrelation than lowtemperature folded states. To estimate an overall energy decorrelation time to apply to all states, we fit the individual decorrelation times to a normal distribution, and chose the time which yields a cumulative probability distribution value of (2n replica -1)/(2n replica ).