Livingstone J R, Spolar R S, Record M T
Department of Biochemistry, University of Wisconsin, Madison 53706.
Biochemistry. 1991 Apr 30;30(17):4237-44. doi: 10.1021/bi00231a019.
Protein folding and the transfer of hydrocarbons from a dilute aqueous solution to the pure liquid phase are thermodynamically similar in that both processes remove nonpolar surface from water and both are accompanied by anomalously large negative heat capacity changes. On the basis of a limited set of published surface areas, we previously proposed that heat capacity changes (delta C degrees p) for the transfer of hydrocarbons from water to the pure liquid phase and for the folding of globular proteins exhibit the same proportionality to the reduction in water-accessible nonpolar surface area (delta Anp) [Spolar, R.S., Ha, J.H., & Record, M.T., Jr. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 8382-8385]. The consequence of this proposal is that the experimental delta C degrees p for protein folding can be used to obtain estimates of delta Anp and of the contribution to the stability of the folded state from removal of a nonpolar surface from water. In this paper, a rigorous molecular surface area algorithm [Richmond, T.J. (1984) J. Mol. Biol. 178, 63-89] is applied to obtain self-consistent values of the water-accessible nonpolar surface areas of the native and completely denatured states of the entire set of globular proteins for which both crystal structures and delta C degrees p of folding have been determined and for the set of liquid and liquefiable hydrocarbons for which delta C degrees p of transfer are known. Both processes (hydrocarbon transfer and protein folding) exhibit the same direct proportionality between delta C degrees p and delta Anp. We conclude that the large negative heat capacity changes observed in protein folding and other self-assembly processes involving proteins provide a quantitative measure of the reduction in the water-accessible nonpolar surface area and of the contribution of the hydrophobic effect to the stability of the native state and to protein assembly.
蛋白质折叠以及烃类从稀水溶液转移至纯液相在热力学上具有相似性，因为这两个过程都会使非极性表面脱离水相，并且都伴随着异常大的负热容变化。基于一组有限的已发表表面积数据，我们先前提出，烃类从水相转移至纯液相以及球状蛋白质折叠过程中的热容变化（ΔC°p）与水可及非极性表面积的减少量（ΔAnp）呈现相同的比例关系[Spolar, R.S., Ha, J.H., & Record, M.T., Jr. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 8382 - 8385]。该提议的结果是，蛋白质折叠实验得到的ΔC°p可用于估算ΔAnp，以及通过将非极性表面从水相中移除对折叠态稳定性的贡献。在本文中，我们应用了一种严格的分子表面积算法[Richmond, T.J. (1984) J. Mol. Biol. 178, 63 - 89]，以获得一整套球状蛋白质天然态和完全变性态的水可及非极性表面积的自洽值，这些蛋白质的晶体结构和折叠的ΔC°p均已确定，同时也获得了一组已知转移ΔC°p的液态和可液化烃类的水可及非极性表面积的自洽值。这两个过程（烃类转移和蛋白质折叠）在ΔC°p和ΔAnp之间都呈现相同的直接比例关系。我们得出结论，在蛋白质折叠以及其他涉及蛋白质的自组装过程中观察到的大的负热容变化，为水可及非极性表面积的减少以及疏水作用对天然态稳定性和蛋白质组装的贡献提供了一种定量度量。
