Poland D
Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA.
Biopolymers. 2001 Jan;58(1):89-105. doi: 10.1002/1097-0282(200101)58:1<89::AID-BIP90>3.0.CO;2-7.
Experimental data on the temperature dependence of the heat capacity of proteins can be used to calculate approximate enthalpy distributions for these molecules using the maximum-entropy method. C(p) (T) data is first used to calculate a set of moments of the enthalpy distribution, and these are then used to estimate the enthalpy distribution. If one knows the temperature expansion of the heat capacity through the (n - 2)th power of DeltaT (measured from the expansion center), then this is enough information to calculate the nth moment of the enthalpy distribution. Using four or more moments is in turn enough information to resolve bimodal behavior in the distribution. If the enthalpy distribution of a protein exhibits two distinct peaks, then this is direct experimental confirmation of a two-state mechanism of denaturation, the two peaks corresponding to the enthalpy of the native and unfolded species respectively. If the heat capacity of a protein exhibits a maximum at the denaturation temperature, then there is the possibility that the enthalpy distribution will be bimodal, but the presence of a maximum in the heat capacity is not a sufficient condition for this kind of behavior. We construct a phase diagram in terms of the appropriate variables to indicate when a maximum in the heat capacity will also give rise to bimodal behavior in the enthalpy distribution. We illustrate the phase diagram using literature data for a set of proteins.
蛋白质热容与温度相关性的实验数据可用于通过最大熵方法计算这些分子的近似焓分布。首先使用C(p)(T)数据计算焓分布的一组矩，然后用这些矩来估计焓分布。如果知道热容随温度的展开式，其最高次幂为DeltaT的(n - 2)次幂（从展开中心测量），那么这些信息足以计算焓分布的第n个矩。使用四个或更多矩则足以解析分布中的双峰行为。如果蛋白质的焓分布呈现两个不同的峰，那么这是变性双态机制的直接实验证据，这两个峰分别对应天然态和去折叠态物种的焓。如果蛋白质的热容在变性温度处出现最大值，那么焓分布有可能是双峰的，但热容出现最大值并非这种行为的充分条件。我们根据适当的变量构建相图，以表明热容最大值何时也会导致焓分布出现双峰行为。我们用一组蛋白质的文献数据来说明相图。
