The performance of the Boresch restraints with the force constants fit to simulation were compared to those with all force constants set to the common defaults of 10 or 20 kcal mol -1 Å-2 [rad -2 ], denoted by -10 and -20 (Table ). No significant differences in ∆G o Bound were found compared to when the force constants were fit to simulation, which was unsurprising given that the theoretical independence of the binding free energy with respect to the strength of restraints has been previously confirmed. If there were any improvements in precision or increases in the rate of convergence with the force constants fit to simulation, these were not observed above the noise generated by other sources of error.