Development of empirical molecular interaction models that incorporate hydrophobicity and hydropathy. The HINT paradigm

While molecular mechanics calculates with impressive accuracy the small det ails of molecular structure, even for large proteins and other biological m acromolecules, the gross features of these molecules are almost invariably poorly predicted. Most importantly molecular mechanics force fields do not include entropy. The HINT model, which we have been developing over the pas t several years, is based on the experimental measurement of logP(o/w) , th e partition coefficient for small molecule octanol/water solubilities. Thes e partition coefficients represent a rare direct experimental measurement o f non-covalent interaction that inherently includes entropy and solvation e ffects. This paper reviews the development of the HINT paradigm with illust rations from recent studies.