PREDICTING EQUILIBRIUM PROTEIN FOLDING PATHWAY OF STAPHYLOCOCCAL NUCLEASE

葡萄球菌核酸酶(SNase)的平衡折叠途径 已经使用统计热力学形式进行了近似 利用本机状态的高分辨率结构作为 模板以产生部分折叠状态的大集合。一个 总共163,822个不同的州，从原住民到 完全展开状态包括在分析中。这个 每种状态的概率都是使用经验的 能量学的参数化法。在本文中，预测了 将每个残基的表观折叠常数与天然的 37℃下核磁共振测得的态氢交换保护因子 这一形式主义准确地预测了114出的保护系数 在137个残基中(83%)。两者之间的区别 理论自由能和实验自由能平均为0.14千卡/摩尔。在……里面 特别是，研究表明，蛋白质中最不稳定的区域 涉及第三条b链之后的环区，向上穿过 螺旋1的前半部分(残基41-58)和之间的环区 第四和第五条b链(残基77-88)。最稳定的 蛋白质的区域包括那些有助于 B桶和剩余的螺旋结构。考试的结果 残基折叠概率作为微观度的函数 折叠的结果表明蛋白质中最稳定的区域 在具有高度结构的分子中并不一定 与分子中最稳定的区域相对应 结构(&lt；10%)。对于后一种情况，本地倾向占主导地位 在前一案例中合作时的折叠概率 当地地区之间的互动有助于增加 组合稳定性。

The equilibrium folding pathway of Staphylococcal Nuclease (SNase) has been approximated using a statistical thermodynamic formalism that utilizes the high resolution structure of the native state as a template to generate a large ensemble of partially folded states. A total of 163,822 different states ranging from the native to the completely unfolded state were included in the analysis. The probability of each state was estimated using an empirical parametrization of the energetics. In this paper the predicted apparent folding constants per residue are compared to the native state hydrogen exchange protection factors obtained by NMR at 37 C. This formalism predicts accurately the protection factors of 114 out of 137 residues (83 %) in the protein. The difference between predicted and experimental free energies averages 0.14 kcal/mol. In particular, it is shown that the least stable regions of the protein involve the loop region following the third b strand up through the first half of helix 1 (residues 41-58), and the loop region between the fourth and fifth b strands (residues 77-88). The most stable regions of the protein involve those residues which contribute to the b barrel and the remaining helical structure. Examination of the residue folding probabilities as a function of the microscopic degree of folding shows that the regions of the protein which are most stable in molecules with a high degree of structure do not necessarily correspond to the most stable regions in molecules with little structure (< 10 %). For the latter case local propensities dominate folding probabilities while in the former case cooperative interactions between local regions serve to increased the combined stabilities.