THE PRINCIPLES THAT GOVERN PROTEIN FOLDING--THE SECOND HALF OF THE GENETIC CODE

基于以前的研究，我们假设，折叠后， 例如，葡萄球菌核酸酶的原子间 相互作用将在全球范围内耦合，以产生额外的力量， 改变折叠和展开之间的平衡， 折叠，这种耦合将发生在一条线的基础上 在三个原子之间形成一条闭合曲线 空间结构 这种全球性的调制的结果 耦合将是从一个 构象能态转换成另一个构象能态， 约束原子位置的力的变化 结构。 我们用一个模型来检验这个假设 由血红素形成的I型和II型两种同分异构络合物系统 片段（1 - 38）H和马细胞色素c的脱辅基蛋白。 我们 研究1）相互转化的动力学和热力学 在络合物亚铁（1 - 38）H-（1 - 104）的I型和II型之间; 2） CO结合群体; 3）解离速率 络合物ferri-和ferro（1 - 38）H-（39 - 104）（模拟II型 4.695mm吸收带的热跃迁 和生物活性。 结果表明：a）相互转化 在两种络合物形式之间，出现（1 - 38）H-（104） 不经过离解，与焓有关 有利于类型I的变化和有利于类型II的熵变; B） CO结合群体与II型相关;和 血红素状态似乎影响热力学关系 两种形式之间。 结果表明，"内- 铁型I和铁型II形式之间的分子"翻转将 建立了这两个明显的玻尔兹曼分布 不同的能量状态，I型形式具有更强的 原子间相互作用和II型更明显的内部 议案 由于该模型是一个精确的两态系统， 对于同分异构复合物，测得的焓和熵 变化可以被明确地解释为与变化有关， 内部运动，即约束原子的力的变化 分布在结构中的位置，揭示了新的主要来源 蛋白质折叠的焓变和熵变。

Based on the previous studies, we hypothesize that after folding of, for example, staphylococcal nuclease the interatomic interactions would be globally coupled to generate extra force for shifting the equilibrium between folding and unfolding in favor of folding and that such coupling would occur on the basis of a line of contacting atoms forming a closed curve in the three- dimensional structure. A result of modulation of this global coupling would be that transformation from one of the conformational energy states to another would involve concerted changes of forces constraining the atomic positions throughout the structure. We have tested this hypothesis using a model system of two isomeric complexes type I and II formed from heme fragment (1-38)H and apoprotein of horse cytochrome c. We investigated 1) kinetics and thermodynamics of interconversion between type I and II forms of complex ferro(1-38)H-(1-104); 2) the CO-binding population; 3) the rate of dissociation of complexes ferri- and ferro(1-38)H-(39-104) (mimicking type II form); and 4) thermal transition of the 695mm absorption band and biological activity. The results indicate a) interconversion between the two forms of complex ferro(1-38)H-(104) occurs without going through dissociation and is associated with enthalpy change favoring type I and entropy change favoring type II; b) the CO-binding population correlates with type II; and c) the redox state of heme appears to influence the thermodynamic relatinship between the two forms. The results suggest that "intra- molecular" flip between ferro-type I and ferro-type II forms would establish the Boltzmann distribution of these two distinctly different energy states, type I form having more strengthened interatomic interactions and type II more pronounced internal motion. Since this model is an exact two-state system by virtue of isomeric complexes, the measured enthalpy and entropy changes can be unambiguously interpreted as relating to changes of internal motion, i.e. changes of forces constraining atomic positions distributed in the structure, revealing new major sources of enthalpy and entropy changes for protein folding.