title: Hydrophobicity regained.
abstract: A widespread practice is to use free energies of transfer between organic solvents and water (delta G0transfer to define hydrophobicity scales for the amino acid side chains. A comparison of four delta G0transfer scales reveals that the values for hydrogen-bonding side chains are highly dependent on the non-aqueous environment. This property of polar side chains violates the assumptions underlying the paradigm of equating delta G0transfer with hydrophobicity or even with a generic solvation energy that is directly relevant to protein stability and ligand binding energetics. This simple regaining of the original concept of hydrophobicity reveals a flaw in approaches that use delta G0transfer values to derive generic estimates of the energetics of the burial of polar groups, and allows the introduction of a "pure" hydrophobicity scale for the amino acid residues.
authors.affiliation: Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, New York 14853, USA. pak4@cornell.edu
authors.forename: P A
authors.initials: PA
authors.lastname: Karplus
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D017510:Protein Folding; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D000596:Amino Acids; D012997:Solvents; D014867:Water