Eggimann Becky L, Vostrikov Vitaly V, Veglia Gianluigi, Siepmann J Ilja
Department of Chemistry, Chemical Theory Center, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455, USA.
Molecular Biology and Biophysics, University of Minnesota, 321 Church St. SE, Minneapolis, MN 55455, USA.
Theor Chem Acc. 2013 Oct 1;132(10):1388. doi: 10.1007/s00214-013-1388-y.
We present a fast and simple protocol to obtain moderate-resolution backbone structures of helical proteins. This approach utilizes a combination of sparse backbone NMR data (residual dipolar couplings and paramagnetic relaxation enhancements) or EPR data with a residue-based force field and Monte Carlo/simulated annealing protocol to explore the folding energy landscape of helical proteins. By using only backbone NMR data, which are relatively easy to collect and analyze, and strategically placed spin relaxation probes, we show that it is possible to obtain protein structures with correct helical topology and backbone RMS deviations well below 4 Å. This approach offers promising alternatives for the structural determination of proteins in which nuclear Overha-user effect data are difficult or impossible to assign and produces initial models that will speed up the high-resolution structure determination by NMR spectroscopy.
我们提出了一种快速且简单的方案，用于获取螺旋蛋白的中等分辨率主链结构。该方法结合了稀疏的主链核磁共振数据（剩余偶极耦合和顺磁弛豫增强）或电子顺磁共振数据，以及基于残基的力场和蒙特卡罗/模拟退火方案，以探索螺旋蛋白的折叠能量景观。通过仅使用相对易于收集和分析的主链核磁共振数据，以及策略性放置的自旋弛豫探针，我们表明有可能获得具有正确螺旋拓扑结构且主链均方根偏差远低于4 Å的蛋白质结构。这种方法为那些难以或无法归属核Overhauser效应数据的蛋白质结构测定提供了有前景的替代方案，并产生初始模型，从而加快通过核磁共振光谱法进行的高分辨率结构测定。
