Exploring the folding free energy surface of a three-helix bundle protein
Exploring the folding free energy surface of a three-helix bundle protein
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DOI：
10.1073/pnas.94.19.10161
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发表时间：
1997-09-16
影响因子：
11.1
通讯作者：
Boczko, EM
中科院分区：
文献类型：
--
作者：
Guo, ZY;Brooks, CL;Boczko, EM
基于第一性原理计算方法，研究了葡萄球菌蛋白A片段B的46个残基的小螺旋快速折叠蛋白质的多维自由能曲面。探讨了塌陷与三级构造形成的关系，以及塌陷与二级构造形成的顺序。我们还观察到在这种坍缩状态下天然螺旋的两种不同分布（R-g约为12埃，一种含有约20%的天然螺旋氢键，另一种含有约70%的天然螺旋氢键）。前者对应于局部最小值。从该亚稳态到自然态的势垒约为2 k（B）T。在后一种情况下，折叠本质上是一个涉及拓扑组装的下坡过程。此外，我们还研究了三个螺旋之间二级结构的形成顺序，观察到螺旋Ⅰ和螺旋Ⅱ的二级结构是协同形成的，螺旋Ⅲ的二级结构是在螺旋Ⅰ和螺旋Ⅱ都形成一定的二级结构后才开始形成的，并与理论和实验结果进行了比较。
The multidimensional free energy surface for a small fast folding helical protein is explored based on first-principle calculations, The model represents the 46-residue segment from fragment B of staphylococcal protein A. The relationship between collapse and tertiary structure formation, and the order of collapse and secondary structure formation, are investigated. We find that the initial collapse process gives rise to a transition state with about 30% of the native tertiary structure and 50-70% of the native helix content, We also observe two distinct distributions of native helix in this collapsed state (R-g approximate to 12 Angstrom, one with about 20% of the native helical hydrogen bonds, the other with near 70%. The former corresponds to a local minimum. The barrier from this metastable state to the native state is about 2 k(B)T. In the latter case, folding is essentially a downhill process involving topological assembly. In addition, the order of formation of secondary structure among the three helices is examined, We observe cooperative formation of the secondary structure in helix I and helix II, Secondary structure in helix III starts to form following the formation of certain secondary structure in both helix I and helix II, Comparisons of our results with those from theory and experiment are made.