The alternative binding mode proposed here is stable throughout the GAP simulation, which is a good indication that GAP is able to capture a range of conformations of this flexible molecule. The alternative binding mode is not stable in the MM simulation, and there is a rotation of the pyridine ring of 3BPA, which breaks the hydrogen bond between the amine group and the backbone of residue Pro374. However, in the duplicate MM run (Figure ), the bound conformation is stable for longer before the hydrogen bond is broken, and so longer simulations would be required to establish the equilibrium populations of these binding modes.