From an initial set of restraining simulations, two binding poses were identified (Figure ) which interconverted slowly on the timescale of the simulations (6 ns). To allow comparison of different restraints for a single binding pose, all restraints were fit to binding pose A, other than a single set of Boresch restraints which was fit to pose B. The calculation for pose B was carried out to allow comparison to the experimental free energy of binding.