latter is favored by ANI-2x. The main differences between the MM and the ANI-2x level of theory for hp7 can be best seen in the 1-D torsion scans (Figure ). First, for χ 2 = ±180 • , there is an energy difference of ≈ 2k B T in the height of the local minimum between the NNP and MM potential at χ 1 = ±180 • (left plot in Figure ). Second, when transitioning along χ 2 from ±180 • to 0 • degrees at fixed χ 1 = 0 • , at the MM level of theory χ 2 = 0 • is a maximum. However, at the NNP level of theory (right plot in Figure ), there is a local minimum at χ 2 = 0 • . This leads to different behavior around the global minimum at ±180 • In panel 1, we see that the NNP→MM switch resulting in the most negative work value starts and ends in the global energy minimum of both surfaces (χ