Extracting hydrophobicity parameters from solute partition and protein mutation unfolding experiments

被引:25
作者
Vajda, S
Weng, ZP
DeLisi, C
机构
[1] Department of Biomedical Engineering, Boston University, Boston, MA 02215
来源
PROTEIN ENGINEERING | 1995年 / 8卷 / 11期
关键词
hydrophobicity parameters; partition experiments; protein stability; residue mutation; transfer free energy;
D O I
10.1093/protein/8.11.1081
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hydrophobicity values for amino acids obtained from protein unfolding experiments are about twice as large as those obtained from data on the partitioning of amino acids between water and octanol, Quantitative analyses of several data sets, presented here, indicate that the difference is best explained by the most direct hypothesis, i,e, that the environment of hydrophobic groups in the interior of a protein is poorly modeled by octanol, Instead, we propose-and provide supporting evidence-that hydrocarbons are a more suitable model, First, we reanalyze data from both solute partitioning and protein unfolding experiments, taking account of the effects that were omitted previously, by introducing a volume dependence in the former and a full free energy analysis in the latter, Both changes in evaluation methodology decrease the discrepancy, but the differences remain substantial, The hydrophobicity parameter 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 interior is also suggested more directly by an analysis of the contact environment of hydrophobic side chains in mutation/unfolding experiments, which have polar contact areas that are <2% of the total.
引用
收藏
页码:1081 / 1092
页数:12
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