According to the simulations, the flexible phosphopeptides have more favorable binding enthalpies than their less flexible, constrained analogs, in disagreement with the experimental data. Although longer simulations would be useful to further reduce numerical uncertainty, the convergence achieved here is good enough that the discrepancy relative to experiment appears to be robust. Assuming that setup issues, such as protonation states, have been correctly handled, this result suggests that replicating experimental results will require a more accurate force field. Prior simulations of systems drawn from the same experimental study , but using the more detailed AMOEBA force field , successfully replicated the experimental trend that the constrained peptides bind with more favorable enthalpies than the flexible ones . Nonetheless, the prior AMOEBA results are not more accurate in absolute terms: the absolute deviations of the AMOEBA results from experiment, 7.8 and 2.1 kcal/mol for cpYVN-fpYVN and cpYIN-fpYIN, respectively, are essentially the same as those observed here for cpYVN-fpYVN and cpYQN-fpYQN, 7.9 and 2.4 kcal/mol, respectively. As a consequence, it is not clear that this comparison with experiment can be interpreted as supporting the accuracy of simulations with AMOEBA over the simpler force field used here.