Murphy K P, Gill S J
Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309-0215.
J Mol Biol. 1991 Dec 5;222(3):699-709. doi: 10.1016/0022-2836(91)90506-2.
Analysis of thermodynamic data on the dissolution of solid cyclic dipeptides into water in terms of group additivity provides a rationale for the enthalpy and entropy convergence temperatures observed for small globular protein denaturation and the dissolution of model compounds into water. Convergence temperatures are temperatures at which the extrapolated enthalpy or entropy changes for a series of related compounds take on a common value. At these temperatures (TH* and TS*) the apolar contributions to the corresponding thermodynamic values (delta H degrees and delta S degrees) are shown to be zero. Other contributions such as hydrogen bonding and configurational effects can then be evaluated and their quantitative effects on the stability of globular proteins assessed. It is shown that the denaturational heat capacity is composed of a large positive contribution from the exposure of apolar groups and a significant negative contribution from the exposure of polar groups in agreement with previous results. The large apolar contribution suggests that a liquid hydrocarbon model of the hydrophobic effect does not accurately represent the apolar contribution to delta H degrees of denaturation. Rather, significant enthalpic stabilizing contributions are found to arise from peptide groups (hydrogen bonding). Combining the average structural features of globular proteins (i.e. number of residues, fraction of buried apolar groups and fraction of hydrogen bonds) with their specific group contributions permits a first-order prediction of the thermodynamic properties of proteins. The predicted values compare well with literature values for cytochrome c, myoglobin, ribonuclease A and lysozyme. The major thermodynamic features are described by the number of peptide and apolar groups in a given protein.
根据基团加和性对固体环状二肽在水中溶解的热力学数据进行分析，为观察到的小球状蛋白质变性以及模型化合物在水中溶解的焓和熵收敛温度提供了理论依据。收敛温度是一系列相关化合物外推的焓变或熵变取共同值时的温度。在这些温度（TH和TS）下，对相应热力学值（ΔH°和ΔS°）的非极性贡献被证明为零。然后可以评估其他贡献，如氢键和构型效应，并评估它们对球状蛋白质稳定性的定量影响。结果表明，变性热容量由非极性基团暴露产生的大的正贡献和极性基团暴露产生的显著负贡献组成，这与先前的结果一致。大的非极性贡献表明，疏水效应的液态烃模型不能准确代表对变性ΔH°的非极性贡献。相反，发现肽基团（氢键）产生了显著的焓稳定贡献。将球状蛋白质的平均结构特征（即残基数量、埋藏非极性基团的比例和氢键的比例）与其特定的基团贡献相结合，可以对蛋白质的热力学性质进行一阶预测。预测值与细胞色素c、肌红蛋白、核糖核酸酶A和溶菌酶的文献值比较良好。给定蛋白质中的肽基团和非极性基团数量描述了主要的热力学特征。
