T4 LYSOZYME MUTANTS STRUCT THERMODYNAMICS: COOPERATIVE INTERACTION STRUCT MAP

结构参数化法的最新发展 蛋白质折叠的能量学允许将 描述热焓、熵和热容的函数 (即吉布斯能量的各个分量)变成一个 统计热力学的形式，描述的分布 平衡条件下的构象状态。这样做的目的是 方法是用计算机构建一个大型的 构象状态，然后推导出最可能的布居 分布(即，最大范围内的分布 实验观测数据阵列)。这一分析已被应用于 T4溶菌酶的4个不同突变体(S44A、S44G、V131A、V131G)。它 结果表明，结构参数化能很好地预测 蛋白质的稳定性和突变的影响。整个 计算了每个残基的折叠常数集 变种人。在所有情况下，突变的影响都会传播到 突变位点本身通过序列和三维空间。 这种影响会发生，尽管突变是 暴露在溶剂中的部位，不会直接影响 蛋白质。这些结果表明，单一氨基酸突变 在溶剂暴露部位可以用来识别 蛋白质中的协作相互作用。其规模和程度 这些效果和算法的准确性可以通过以下方法进行测试 检测到的核磁共振 氢交换。

The recent development of a structural parameterization of the energetics of protein folding has permitted the incorporation of the functions that describe the enthalpy, entropy, and heat capacity (i.e., the individual components of the Gibbs energy) into a statistical thermodynamic formalism that describes the distribution of conformational states under equilibrium conditions. The goal of this approach is to construct with the computer a large ensemble of conformational states, and then to derive the most probable population distribution (i.e., the distribution that best accounts for a wide array of experimental observables). This analysis has been applied to four different mutants of T4 lysozyme (S44A, S44G, V131A, V131G). It is shown that the structural parameterization predicts well the stability of the protein and the effects of the mutation. The entire set of folding constants per residue has been calculated for each mutant. In all cases the effect of the mutation propagates beyond the mutation site itself through sequence and three dimensional space. This effect occurrs despite the fact that the mutations are solvent-exposed sites and do not directly effect other interactions in the protein. These results suggest that single amino acid mutations at solvent exposed sites can be used to identify the extent of cooperative interactions in proteins. The magnitude and extent of these effects and the accuracy of the algorithm can be tested by means of NMR detected hydrogen exchange.