EXTRACTING HYDROPHOBICITY PARAMETERS FROM SOLUTE PARTITION AND PROTEIN MUTATION UNFOLDING EXPERIMENTS

Hydrophobicity values for amino acids obtained from protein unfolding experiments are about twice as large as those obtained from data on th e partitioning of amino acids between water and octanol, Quantitative analyses of several data sets, presented here, indicate that the diffe rence is best explained by the most direct hypothesis, i,e, that the e nvironment of hydrophobic groups in the interior of a protein is poorl y modeled by octanol, Instead, we propose-and provide supporting evide nce-that hydrocarbons are a more suitable model, First, we reanalyze d ata from both solute partitioning and protein unfolding experiments, t aking account of the effects that were omitted previously, by introduc ing a volume dependence in the former and a full free energy analysis in the latter, Both changes in evaluation methodology decrease the dis crepancy, but the differences remain substantial, The hydrophobicity p arameter obtained from side-chain transfers between octanol and water increases from 16.7 to 22 cal/mol/Angstrom(2) while that obtained from protein unfolding decreases from 34.9 to 31.2 cal/mol/Angstrom(2). On the other hand, our analysis of the solubilities of pure hydrocarbons in water provides a hydrophobicity parameter of 30.8 cal/mol/Angstrom (2). This apparent hydrocarbon-like environment of a protein's interio r is also suggested more directly by an analysis of the contact enviro nment of hydrophobic side chains in mutation/unfolding experiments, wh ich have polar contact areas that are <2% of the total.