Ikegami A
Biophys Chem. 1977 Jan;6(2):117-30. doi: 10.1016/0301-4622(77)87002-6.
A general theory of the structural changes and fluctuations of proteins has been proposed based on statistical thermodynamic considerations at the chain level. The "structure" of protein was assumed to be characterized by the state of secondary bonds between unique pairs of specific sites on peptide chains. Every secondary bond changes between the bonded and unbonded states by thermal agitation and the "structure" is continuously fluctuating. The free energy of the "structural state" that is defined by the fraction of secondary bonds in the bonded state has been expressed by the bond energy, the cooperative interaction between bonds, the mixing entropy of bonds, and the entropy of polypeptide chains. The most probable "structural state" can be simply determined by graphical analysis and the effect of temperature or solvent composition on it is discussed. The temperature dependence of the free energy, the probability distribution of structural states and the specific heat have been calculted for two examples of structural change. The theory predicts two different types of structural changes from the ordered to disorderd state, a "structured transition" and a "gradual structural change" with rising temperature. In the "structural transition", the probability distribution has two maxima in the temperature range of transition. In the "gradual structural change", the probabilty distribution has only one maximum during the change. A considerable fraction of secondary bonds is in the unbounded state and is always fluctuating even in the ordered state at room temperature. Such structural flucutations in a single protein molecule have been discussed quantitatively. The theory is extended to include small molecules which bind to the protein molecule and affect the structural state. The changes of structural state caused by specific and non-specific binding and allosteric effects are explained in a unified manner.
基于链水平的统计热力学考量，提出了一种关于蛋白质结构变化和波动的通用理论。蛋白质的“结构”被假定以肽链上特定位点独特对之间的二级键状态为特征。每个二级键通过热搅动在键合态和非键合态之间变化，且“结构”持续波动。由处于键合态的二级键分数定义的“结构状态”的自由能，已通过键能、键之间的协同相互作用、键的混合熵以及多肽链的熵来表示。最可能的“结构状态”可通过图形分析简单确定，并讨论了温度或溶剂组成对其的影响。针对两个结构变化的例子，计算了自由能的温度依赖性、结构状态的概率分布和比热。该理论预测了随着温度升高从有序态到无序态的两种不同类型的结构变化，即“结构转变”和“逐渐结构变化”。在“结构转变”中，概率分布在转变温度范围内有两个最大值。在“逐渐结构变化”中，概率分布在变化过程中只有一个最大值。相当一部分二级键处于未键合状态，即使在室温下的有序态也总是波动的。对单个蛋白质分子中的这种结构波动进行了定量讨论。该理论被扩展以包括与蛋白质分子结合并影响结构状态的小分子。以统一的方式解释了由特异性和非特异性结合以及别构效应引起的结构状态变化。
