Structure-derived hydrophobic potential. Hydrophobic potential derived from X-ray structures of globular proteins is able to identify native folds.

We present a model for the hydrophobic interaction in globular proteins that is based entirely on an analysis of known X-ray structures. This structure-derived hydrophobic force is identified as the strongest among the non-covalent interactions that stabilize native folds. The functional form of the hydrophobic interaction is found to be linear, corresponding to a constant force along the observable distance range (5 to 70 A). The parameters of the hydrophobic amino acid pair potentials yield a structure-derived hydrophobicity scale that correlates strongly with scales derived by a variety of complementary approaches. We demonstrate that the structure-derived hydrophobic interaction alone is able to distinguish a substantial number of native conformations from a large pool of misfolded structures.