We note that in the systems considered in this work, the volume of the simulation cell is not specified, and so ∆G is equivalent to the change in Helmholtz free energy (∆A), and ∆H is equivalent to the change in internal energy (∆U ). Uncertainty in ∆G ij (T ) can be computed from the covariance matrix returned by pymbar, or by the bootstrapping scheme implemented in cg_openmm. From the free energy data as a function of temperature, entropy change of folding (∆S) and enthalpy change of folding (∆H) are computed by evaluating the derivative of a cubic spline fit to the ∆G vs T curve: