Hydrophobic regions on protein surfaces

Abstract

Changes in solvation of ligand and receptor molecules during docking contribute essentially to the total energy of the binding process. In aqueous solution, the exposure of large hydrophobic surface regions is energetically unfavourable. Therefore, such surface elements are preferential binding sites and shielded from bulk water in the docking interface. In this review, physical approximations based on properties of the hydration shell structures and leading to the surface model of solvation are systematically analysed. The idea of atomic solvation parameters is shown to be applicable only to hydrophobic parts of the molecular surface. Additionally, the traditional concept of the solvent-accessible surface overestimates the hydrophobicity of molecules with both polar and non-polar solvent-exposed atomic groups. Only those hydrophobic surface regions that are not covered by first hydration shell water molecules can interact with bulk water. Methods for computing hydrophobic surface regions both with explicit models of water shells and with an incremental radial expansion of solvent-accessible polar atoms are considered in detail. The latter technique is shown to provide an easy and quick view of the likely hydrophobic surface regions available for hydrophobic ligand binding. As a literature review revealed, the specific hydrophobic surface energy appears in the range 12–30 cal/(molA2), but the exact value applicable for conformational and docking studies is still a matter of debate.