It is important to note that the agreement between the experimental and simulated R g values using θ 1 is not perfect even for the training IDPs. Given that the reweighted ensemble Z ME 0 matches the experimental data exactly for the training IDPs, this suggests that the ensemble Z 1 does not match the reweighted ensemble Z ME 0 exactly, although the hydrophobicity parameters θ 1 are optimized using Z ME 0 as the target. A primary reason for the discrepancy is that the functional form of the hydrophobic interaction in the HPS-Urry model is not expressive enough to exactly reproduce the reweighted ensemble Z ME 0 .