Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts 02139-4307, USA.
J Am Chem Soc. 2011 Jul 6;133(26):10022-5. doi: 10.1021/ja203075p. Epub 2011 Jun 13.
Thermal fluctuations cause proteins to adopt an ensemble of conformations wherein the relative stability of the different ensemble members is determined by the topography of the underlying energy landscape. "Folded" proteins have relatively homogeneous ensembles, while "unfolded" proteins have heterogeneous ensembles. Hence, the labels "folded" and "unfolded" represent attempts to provide a qualitative characterization of the extent of structural heterogeneity within the underlying ensemble. In this work, we introduce an information-theoretic order parameter to quantify this conformational heterogeneity. We demonstrate that this order parameter can be estimated in a straightforward manner from an ensemble and is applicable to both unfolded and folded proteins. In addition, a simple formula for approximating the order parameter directly from crystallographic B factors is presented. By applying these metrics to a large sample of proteins, we show that proteins span the full range of the order-disorder axis.
热波动导致蛋白质采取一系列构象，其中不同构象单元的相对稳定性由基础能量景观的形貌决定。“折叠”的蛋白质具有相对均匀的构象单元，而“未折叠”的蛋白质具有异质的构象单元。因此，“折叠”和“未折叠”这两个标签代表了试图对基础构象单元内结构异质性的程度进行定性描述。在这项工作中，我们引入了一个信息论序参数来量化这种构象异质性。我们证明，这个序参数可以从一个构象单元以一种直接的方式进行估计，并且适用于未折叠和折叠的蛋白质。此外，还提出了一个简单的公式，可以直接从晶体学 B 因子来近似这个序参数。通过将这些度量应用于大量的蛋白质，我们表明蛋白质跨越了整个有序-无序轴的范围。
