All-atom molecular dynamics simulations of spin labelled double and single-strand DNA for EPR studies.
All-atom molecular dynamics simulations of spin labelled double and single-strand DNA for EPR studies.
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DOI：
10.1039/c7cp08625c
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发表时间：
2018-05
期刊：
影响因子：
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通讯作者：
Christopher C. Prior;L. Danilāne;V. Oganesyan
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文献类型：
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作者：
Christopher C. Prior;L. Danilāne;V. Oganesyan
我们报告的第一个应用程序的完全原子分子动力学（MD）模拟自旋标记的DNA的电子顺磁共振（EPR）谱的预测。两种结构不同的DNA自旋探针的模型与刚性或柔性的位置的氮氧基团的碱基对，在实验研究中采用以前，已经开发。通过MD-EPR联合模拟方法的应用，我们的目标是：首先，提供一个测试床对一个敏感的光谱技术最近开发的改进版本的parmbsc 1力场的MD建模的DNA。预测的EPR谱与文献中的实验结果吻合较好，从而证实了目前采用的DNA力场的准确性。第二，提供一个定量的解释运动的贡献到双链体和单链DNA片段的自旋探针的动力学，并分析其对局部DNA结构的扰动效应。最后，MD和EPR的组合，使我们能够测试的应用程序的无模型（MF）的方法加上磁张量的部分平均的EPR谱的DNA系统的模拟的有效性，通过比较所得的EPR谱直接从MD轨迹模拟。基于M-F的EPR模拟方法相对于直接传播技术的优点在于，它需要可以从较短的MD轨迹计算的运动参数和阶数参数。MD-EPR方法可用于预测和解释具有新型自旋标记的高阶DNA结构的EPR谱。
We report the first application of fully atomistic molecular dynamics (MD) simulations to the prediction of electron paramagnetic resonance (EPR) spectra of spin labelled DNA. Models for two structurally different DNA spin probes with either the rigid or flexible position of the nitroxide group in the base pair, employed in experimental studies previously, have been developed. By the application of the combined MD-EPR simulation methodology we aimed at the following. Firstly, to provide a test bed against a sensitive spectroscopic technique for the recently developed improved version of the parmbsc1 force field for MD modelling of DNA. The predicted EPR spectra show good agreement with the experimental ones available from the literature, thus confirming the accuracy of the currently employed DNA force fields. Secondly, to provide a quantitative interpretation of the motional contributions into the dynamics of spin probes in both duplex and single-strand DNA fragments and to analyse their perturbing effects on the local DNA structure. Finally, a combination of MD and EPR allowed us to test the validity of the application of the Model-Free (M-F) approach coupled with the partial averaging of magnetic tensors to the simulation of EPR spectra of DNA systems by comparing the resultant EPR spectra with those simulated directly from MD trajectories. The advantage of the M-F based EPR simulation approach over the direct propagation techniques is that it requires motional and order parameters that can be calculated from shorter MD trajectories. The reported MD-EPR methodology is transferable to the prediction and interpretation of EPR spectra of higher order DNA structures with novel types of spin labels.