Microsecond dynamics in proteins by two-dimensional ESR: Predictions
Microsecond dynamics in proteins by two-dimensional ESR: Predictions
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DOI：
10.1063/5.0008094
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发表时间：
2020-06-07
影响因子：
4.4
通讯作者：
Freed, Jack H.
中科院分区：
文献类型：
--
作者：
Gupta, Pranav;Liang, Zhichun;Freed, Jack H.
二维电子-电子双共振（2D-ELDOR）提供了对分子运动的广泛了解。最近的发展允许在更高的频率（95 GHz）的实验提供分子取向分辨率，使运动的性质更清晰的描述。在这项工作中，提供了模拟的蛋白质内的域运动的例子，它们本身在溶液中缓慢翻滚。这些显示了交换交叉峰的性质，这些交叉峰被预测为在真实的时间内从这样的畴运动发展。然而，我们发现，现有的理论方法计算2D-ELDOR实验在很宽的运动范围开始严重失败时，适用于非常缓慢的运动特性的蛋白质溶液。一个原因是未能获得准确的特征向量和特征值的复杂的对称随机刘维尔矩阵描述的实验时，计算的有效的Lanczos算法的范围内的非常缓慢的运动。另一个可能更严重的问题是，这些矩阵是“非正态”的，因此对于非常慢的运动范围，即使严格的对角化算法也不能产生正确的特征值和特征向量。我们采用的算法，克服了这两个问题，并导致有效的2D-ELDOR预测，甚至接近刚性极限的运动。他们被用来描述在95 GHz的2D-ELDOR的交叉峰的发展为一个特定的情况下的域运动。
Two-dimensional electron-electron double resonance (2D-ELDOR) provides extensive insight into molecular motions. Recent developments permitting experiments at higher frequencies (95 GHz) provide molecular orientational resolution, enabling a clearer description of the nature of the motions. In this work, simulations are provided for the example of domain motions within proteins that are themselves slowly tumbling in solution. These show the nature of the exchange cross-peaks that are predicted to develop in real time from such domain motions. However, we find that the existing theoretical methods for computing 2D-ELDOR experiments over a wide motional range begin to fail seriously when applied to very slow motions characteristic of proteins in solution. One reason is the failure to obtain accurate eigenvectors and eigenvalues of the complex symmetric stochastic Liouville matrices describing the experiment when computed by the efficient Lanczos algorithm in the range of very slow motion. Another, perhaps more serious, issue is that these matrices are "non-normal," such that for the very slow motional range even rigorous diagonalization algorithms do not yield the correct eigenvalues and eigenvectors. We have employed algorithms that overcome both these issues and lead to valid 2D-ELDOR predictions even for motions approaching the rigid limit. They are utilized to describe the development of cross-peaks in 2D-ELDOR at 95 GHz for a particular case of domain motion.