HYDROPHOBIC REGIONS ON PROTEIN SURFACES - DEFINITION BASED ON HYDRATION SHELL STRUCTURE AND A QUICK METHOD FOR THEIR COMPUTATION

The hydrophobic part of the solvent-accessible surface of a typical mo nomeric globular protein consists of a single, large interconnected re gion formed from faces of apolar atoms and constituting similar to 60% of the solvent-accessible surface area, Therefore, the direct delinea tion of the hydrophobic surface patches on an atom-wise basis is impos sible. Experimental data indicate that, in a two-state hydration model , a protein can be considered to be unified with its first hydration s hell in its interaction with bulk water, We show that, if the surface area occupied by water molecules bound at polar protein atoms as gener ated by AUTOSOL is removed, only about two-thirds of the hydrophobic p art of the protein surface remains accessible to bulk solvent. Moreove r, the organization of the hydrophobic part of the solvent-accessible surface experiences a drastic change, such that the single interconnec ted hydrophobic region disintegrates into many smaller patches, i.e. t he physical definition of a hydrophobic surface region as unoccupied b y first hydration shell water molecules can distinguish between hydrop hobic surface clusters and small interconnecting channels, It is these remaining hydrophobic surface pieces that probably play an important role in intra- and intermolecular recognition processes such as ligand binding, protein folding and protein-protein association in solution conditions, These observations have led to the development of an accur ate and quick analytical technique for the automatic determination of hydrophobic surface patches of proteins, This technique is not aggrava ted by the limiting assumptions of the methods for generating explicit water hydration positions, Formation of the hydrophobic surface regio ns owing to the structure of the first hydration shell can be computat ionally simulated by a small radial increment in solvent-accessible po lar atoms, followed by calculation of the remaining exposed hydrophobi c patches, We demonstrate that a radial increase of 0.35-0.50 Angstrom resembles the effect of tightly bound water on the organization of th e hydrophobic part of the solvent-accessible surface.