Biochemistry Department, Stanford University Medical Center, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1670-3. doi: 10.1073/pnas.1220825110. Epub 2013 Jan 14.
The hydrophobic free energy in current use is based on transfer of alkane solutes from liquid alkanes to water, and it has been argued recently that these values are incorrect and should be based instead on gas-liquid transfer data. Hydrophobic free energy is measured here by gas-liquid transfer of hydrocarbon gases from vapor to water. The new definition reduces more than twofold the values of the apparent hydrophobic free energy. Nevertheless, the newly defined hydrophobic free energy is still the dominant factor that drives protein folding as judged by ΔCp, the change in heat capacity, found from the free energy change for heat-induced protein unfolding. The ΔCp for protein unfolding agrees with ΔCp values for solvating hydrocarbon gases and disagrees with ΔCp for breaking peptide hydrogen bonds, which has the opposite sign. The ΔCp values for the enthalpy of liquid-liquid and gas-liquid transfer are similar. The plot of free energy against the apparent solvent-exposed surface area is given for linear alkanes, but only for a single conformation, the extended conformation, of these flexible-chain molecules. The ability of the gas-liquid hydrophobic factor to predict protein stability is tested and reasonable agreement is found, using published data for the dependences on temperature of the unfolding enthalpy of ribonuclease T1 and the solvation enthalpies of the nonpolar and polar groups.
目前使用的疏水自由能是基于烷烃溶质从液态烷烃向水中的转移，最近有人认为这些值是不正确的，应该基于气液转移数据。本文通过烃类气体从蒸气到水的气液转移来测量疏水自由能。新的定义将表观疏水自由能的值降低了两倍多。然而，根据热诱导蛋白质变性的自由能变化发现的热容变化 ΔCp，新定义的疏水自由能仍然是驱动蛋白质折叠的主要因素。蛋白质变性的 ΔCp 值与溶解烃类气体的 ΔCp 值一致，与破坏肽氢键的 ΔCp 值不一致，后者具有相反的符号。液-液和气-液转移的 ΔCp 值相似。对于线性烷烃，给出了自由能与表观溶剂暴露表面积的关系图，但仅适用于这些柔性链分子的单一构象，即伸展构象。使用已发表的核糖核酸酶 T1 变性焓随温度的依赖性和非极性和极性基团的溶剂化焓的数据，测试了气-液疏水因子预测蛋白质稳定性的能力，并发现了合理的一致性。
