Novel methods for secondary structure determination using low wavelength (VUV) circular dichroism spectroscopic data
Novel methods for secondary structure determination using low wavelength (VUV) circular dichroism spectroscopic data
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DOI：
10.1186/1471-2105-7-507
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发表时间：
2006-11-17
影响因子：
3
通讯作者：
Wallace, B. A.
中科院分区：
文献类型：
--
作者：
Lees, Jonathan G.;Miles, Andrew J.;Wallace, B. A.
背景：圆二色谱（CD）是一种广泛用于研究溶液中蛋白质结构的方法。现代同步辐射CD（SRCD）仪器具有比传统的实验室CD仪器高得多的光子通量，因此能够常规地测量CD数据到低得多的波长。最近，已经产生了一个新的已知结构蛋白质SRCD光谱参考数据集，旨在涵盖二级结构和折叠空间，其中包括低波长（真空紫外- VUV）数据。然而，用于从CD数据计算蛋白质二级结构的现有算法尚未被设计为最佳地利用这些低波长数据中的附加信息。在这项研究中，我们通过检查现有的算法和二级结构分配方案，优化了基于低波长CD数据的二级结构计算方法，然后开发新的方法，这些方法在预测准确性方面有了明显的改进，特别是对于β-折叠组分。我们进一步表明，如果蛋白质浓度的精确测量，因此光谱幅度，是不可用的，包括低波长数据将显着改善分析。然而，我们也证明了新的参考数据集，方法和分配也可以提高传统的圆二色性数据的分析，即使低波长的数据是不可用的。结论：VUV CD数据包括重要的信息，蛋白质结构，可以利用所描述的算法和方法。
Background: Circular Dichroism (CD) spectroscopy is a widely used method for studying protein structures in solution. Modern synchrotron radiation CD (SRCD) instruments have considerably higher photon fluxes than do conventional lab-based CD instruments, and hence have the ability to routinely measure CD data to much lower wavelengths. Recently a new reference dataset of SRCD spectra of proteins of known structure, designed to cover secondary structure and fold space, has been produced which includes low wavelength (vacuum ultraviolet - VUV) data. However, the existing algorithms used to calculate protein secondary structures from CD data have not been designed to take optimal advantage of the additional information in these low wavelength data.Results: In this study, we have optimised secondary structure calculation methods based on the low wavelength CD data by examining existing algorithms and secondary structure assignment schemes, and then developing new methods which have produced clear improvements in prediction accuracy, especially for beta-sheet components. We have further shown that if precise measurements of protein concentrations, and therefore spectral magnitudes, are not available, the inclusion of the low wavelength data will significantly improve the analyses. However, we have also demonstrated that the new reference dataset, methods, and assignments can also improve the analyses of conventional circular dichroism data, even if the low wavelength data is not available.Conclusion: VUV CD data include important information on protein structure which can be exploited with the algorithms and methodologies described.