PREDICTING EQUILIBRIUM PROTEIN FOLDING PATHWAY OF STAPHYLOCOCCAL NUCLEASE

葡萄球菌核酸酶的平衡折叠途径 已经近似使用统计热力学形式主义， 利用原生状态的高分辨率结构作为 模板来生成大量的部分折叠状态。 一 总共有163，822个不同的州，从土著到 完全展开状态包括在分析中。 的 每个状态的概率估计使用经验 能量学的参数化。 本文预测， 每个残基的表观折叠常数与天然的 说明在37 ℃下通过NMR获得的氢交换保护因子。 这种形式主义准确地预测了114个保护因素， 蛋白质中的137个残基（83%）。 的区别 预测的和实验的自由能平均为0.14千卡/摩尔。 在 特别是，研究表明蛋白质的最不稳定区域 涉及第三条B链之后的环区， 螺旋1的前半部分（残基41-58），以及 第四和第五条B链（残基77-88）。 最稳定的 蛋白质的区域涉及那些有助于蛋白质的结构的残基。 B筒和剩余的螺旋结构。 审查 残基折叠概率随微观度的变化 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， 对应于分子中最稳定的区域， 结构（<10%）。 对于后一种情况，地方倾向占主导地位 折叠概率，而在前一种情况下合作 地方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.