Vajda S, Weng Z, DeLisi C
Department of Biomedical Engineering, Boston University, MA 02215, USA.
Protein Eng. 1995 Nov;8(11):1081-92. doi: 10.1093/protein/8.11.1081.
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/Angstrom2, while that obtained from protein unfolding decreases from 34.9 to 31.2 cal/mol/Angstrom2. On the other hand, our analysis of the solubilities of pure hydrocarbons in water provides a hydrophobicity parameter of 30.8 cal/mol/Angstrom2. 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.
从蛋白质解折叠实验中获得的氨基酸疏水性值大约是从氨基酸在水和辛醇之间分配数据中获得的值的两倍。本文展示的对几个数据集的定量分析表明，这种差异最好用最直接的假设来解释，即蛋白质内部疏水基团的环境不能很好地用辛醇来模拟。相反，我们提出——并提供了支持证据——烃类是更合适的模型。首先，我们重新分析了溶质分配和蛋白质解折叠实验的数据，通过在前者中引入体积依赖性以及在后者中进行完整的自由能分析，考虑了之前被忽略的影响。评估方法的这两种变化都减小了差异，但差异仍然很大。从辛醇和水之间的侧链转移获得的疏水性参数从16.7增加到22卡/摩尔/埃²，而从蛋白质解折叠获得的疏水性参数从34.9降低到31.2卡/摩尔/埃²。另一方面，我们对纯烃在水中溶解度的分析得出的疏水性参数为30.8卡/摩尔/埃²。对突变/解折叠实验中疏水侧链接触环境的分析更直接地表明了蛋白质内部这种明显的类烃环境，其极性接触面积占总面积的比例小于2%。
