Hydropathy

Hydropathy is the property of a molecule or a molecular region to interact with water. In biochemistry, it is used to describe the tendency of amino acids and protein segments to be hydrophilic (water-loving) or hydrophobic (water-avoiding). Hydropathy values are derived from scales that assign numerical scores to residues or segments, and the sign and magnitude of these scores depend on the specific scale used; some scales assign higher values to hydrophobic residues, while others use the opposite convention.

One widely used example is the Kyte-Doolittle hydropathy index, which provides a numerical value for each amino acid based on its propensity to be in a hydrophobic environment. Hydropathy analyses often employ hydropathy plots, where the values are averaged over a moving window along a protein sequence. Regions with high hydropathy tend to be buried inside folded proteins or form membrane-spanning helices, whereas hydrophilic regions are more likely to be exposed to aqueous surroundings.

Hydropathy concepts are foundational in protein structure prediction, membrane protein topology, and protein engineering. They are used to infer possible transmembrane segments, predict antigenic regions through related hydrophilicity scales, and guide interpretations of folding patterns. However, hydropathy analyses are approximations; actual behavior depends on three-dimensional structure, tertiary interactions, solvent conditions, and dynamics. Consequently, hydropathy is best viewed as a useful screening and comparative tool rather than a definitive predictor of protein behavior.

Related concepts include hydrophobicity and hydrophilicity, with various scales (such as Eisenberg’s hydrophobicity scale) that provide different yet complementary views of how molecular surfaces interact with water.