Hydrophobicity: is LogP(o/w) more than the sum of its parts?

The empirically calculated parameter LogP(o/w), the log(10) of the coeffici ent for solvent partitioning between 1-octanol and water, has been used to provide the key data for a unique non-covalent interaction force field call ed HINT (Hydropathic INTeractions). This experimentally-derived force field encodes entropic as well as enthalpic information;md also includes some re presentation of solvation and desolvation energetics in biomolecular associ ations. The theoretical basis for the HINT model is discussed. This review includes: 1) discussion of calculational representation of the hydrophobic effect, 2) the rationale for describing the experimental LogP(o/w) based de scriptors used in the HINT force field and model as free energy-like, 3) th e relationship between hydrophobic fragment constants and partial group ele ctrostatic charge, and 4) the implications of structurally-conserved water molecules on free energy of molecular association. Several recent applicati ons of HINT in structure-based and ligand-based drug discovery are reviewed . Finally, future directions in the HINT model development are proposed. (C ) 2000 Editions scientifiques et medicales Elsevier SAS.