Hydrophobicity at the surface of proteins

Anew method is presented to quantitatively estimate and graphically display the propensity of nonpolar groups to bind at the surface of proteins.:It i s based on the calculation of the binding energy, i.e., van der Waals inter action plus protein electrostatic desolvation, of a nonpolar probe sphere r olled over the protein surface, and on the color coding of this quantity on a smooth molecular surface (hydrophobicity map), The method is validated o n ten protein-ligand complexes and is shown to distinguish precisely where polar and nonpolar groups preferentially bind. Comparisons with existing ap proaches, like the display of the electrostatic potential or the curvature, illustrate the advantages and the better predictive power of the present m ethod. Hydrophobicity maps will play an important role in the characterizat ion of binding sites for the large number of proteins emerging from the gen ome projects and structure modeling approaches. Proteins 1999;37:565-575, ( C) 1999 Wiley-Liss, Inc.