Lee B
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Protein Sci. 1993 May;2(5):733-8. doi: 10.1002/pro.5560020505.
Although the hydrophobic effect is generally considered to be one of the most important forces in stabilizing the folded structure of a globular protein molecule, there is a lack of consensus on the precise magnitude of this effect. The magnitude of the hydrophobic effect is most directly measured by observing the change in stability of a protein molecule when an internal hydrophobic residue is mutated to another of smaller size. Results of such measurements have, however, been confusing because they vary greatly and are generally considerably larger than expected from the transfer free energies of corresponding small molecules. In this article, a thermodynamic argument is presented to show (1) that the variation is mainly due to that in the flexibility of the protein molecule at the site of mutation, (2) that the maximum destabilization occurs when the protein at the site of mutation is rigid, in which case the value of the destabilization is approximately given by the work of cavity formation in water, and (3) that the transfer free energy approximately gives the minimum of the range of variations. The best numerical agreements between the small molecule and the protein systems are obtained when the data from the small molecule system are expressed as the molarity-based standard free energies without other corrections.
尽管疏水作用通常被认为是稳定球状蛋白质分子折叠结构的最重要力量之一，但对于这种作用的确切强度，人们尚未达成共识。疏水作用的强度最直接的测量方法是，观察当一个内部疏水残基突变为另一个较小尺寸的残基时，蛋白质分子稳定性的变化。然而，此类测量结果一直令人困惑，因为它们差异很大，而且通常比相应小分子的转移自由能所预期的要大得多。在本文中，我们提出了一个热力学观点来表明：（1）这种差异主要是由于蛋白质分子在突变位点的柔韧性变化所致；（2）当突变位点的蛋白质是刚性的时候，会出现最大程度的去稳定化，在这种情况下，去稳定化的值大约由水中空穴形成的功给出；（3）转移自由能大致给出了变化范围的最小值。当小分子系统的数据表示为基于摩尔浓度的标准自由能且无其他校正时，小分子和蛋白质系统之间能获得最佳的数值一致性。
