EM-Fold: De Novo Folding of α-Helical Proteins Guided by Intermediate-Resolution Electron Microscopy Density Maps
EM-Fold: De Novo Folding of α-Helical Proteins Guided by Intermediate-Resolution Electron Microscopy Density Maps
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DOI：
10.1016/j.str.2009.06.001
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发表时间：
2009-07-15
期刊：
影响因子：
5.7
通讯作者：
Meiler, Jens
中科院分区：
文献类型：
--
作者：
Lindert, Steffen;Staritzbichler, Rene;Meiler, Jens
在中等分辨率（7-10埃）冷冻电子显微镜（cryo-EM）密度图中，α螺旋可以被识别为密度棒，而β链或环区域不容易辨别。我们提出了一种计算蛋白质结构预测算法“EM-折叠”，它通过将预测的α螺旋放入密度棒并在环区域中添加缺失的骨架坐标来解决密度棒连接性的模糊性。在11个已知结构的主要是α-螺旋蛋白质的基准中，在8个病例中确定了天然样模型（rmsd 3.9-7.9埃）。这三次失败可归因于EM-折叠之前的二级结构预测步骤中的不准确性。EM-Fold已应用于来自人腺病毒的蛋白IIIa的类似于6埃分辨率的冷冻-EM密度图。我们报告的第一个拓扑模型的α-螺旋400个残基的N-末端区域的蛋白IIIa。EM-Fold也有可能解释X射线晶体学中的中等分辨率密度图。
In medium-resolution (7-10 angstrom) cryo-electron microscopy (cryo-EM) density maps, alpha helices can be identified as density rods whereas beta-strand or loop regions are not as easily discerned. We are proposing a computational protein structure prediction algorithm "EM-Fold" that resolves the density rod connectivity ambiguity by placing predicted alpha helices into the density rods and adding missing backbone coordinates in loop regions. In a benchmark of 11 mainly alpha-helical proteins of known structure a native-like model is identified in eight cases (rmsd 3.9-7.9 angstrom). The three failures can be attributed to inaccuracies in the secondary structure prediction step that precedes EM-Fold. EM-Fold has been applied to the similar to 6 angstrom resolution cryo-EM density map of protein Illa from human adenovirus. We report the first topological model for the alpha-helical 400 residue N-terminal region of protein Illa. EM-Fold also has the potential to interpret medium-resolution density maps in X-ray crystallography.