Although recent spectroscopic studies of chemically denatured proteins hint at significant nonrandom residual structure, the results of extensive small angle X-ray scattering studies suggest random coil behavior, calling for a coherent understanding of these seemingly contradicting observations. Here, we report the results of a Monte Carlo study of the effects of two types of local structures, a helix and Polyproline II (PPII) helix, on the dimensions of random coil polyalanine chains viewed as a model of highly denatured proteins. With an alpha helix content of 20%, corresponding to the Ramachandran probability of being in the helical basin, experimentally observed radii of gyration are recovered. Experimental radii are similarly recovered at an a helix content of 87%, providing an explanation for the previously puzzling experimental finding that the dimensions of the highly helical methanol-induced unfolded state are experimentally indistinguishable from those of the helix-poor urea-unfolded state. In contrast, the radius of gyration increases monotonically with increasing PPII content, and is always more expanded than the dimensions observed experimentally. These results suggest that PPII is unlikely the sole, dominant preferred conformation for unfolded proteins.
Extended Experimental Inferential Structure Determination Method for Evaluating the Structural Ensembles of Disordered Protein States
表征具有内在或未折叠状态的蛋白质包括结构生物学中的新前沿，需要表征多样和动态的结构集合。我们介绍了一个全面的贝叶斯框架，扩展实验推断结构确定（X-EISD）方法，该方法通过考虑广泛的实验数据和结构的反算模型的不确定性来计算蛋白质结构系综的最大对数似然，包括NMR化学位移，J-耦合，核奥弗豪泽效应，顺磁弛豫增强，残余偶极耦合，和流体动力学半径，单分子荧光Förster共振能量转移效率和小角X射线散射强度曲线。我们将X-EISD应用于drkN SH 3展开状态域，并表明某些实验数据类型比其他类型更有影响力，既消除了结构系综模型，同时也找到了同样可能的无序系综，这些系综具有替代结构特性，将刺激进一步的实验来区分它们。
Spectral analysis of protein backbone geometry reveals abrupt helix--coil boundaries
College of Mathematics and System Science, Xinjiang University（新疆大学数学与系统科学学院）；Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University（新疆大学生命科学与技术学院生物资源与基因工程重点实验室）；Shenzhen X-Institute（深圳X研究院）
