Jin Qiyu, Sorzano Carlos Oscar S, de la Rosa-Trevín José Miguel, Bilbao-Castro José Román, Núñez-Ramírez Rafael, Llorca Oscar, Tama Florence, Jonić Slavica
IMPMC, Sorbonne Universités-CNRS UMR 7590, UPMC Paris 6, MNHN, IRD UMR 206, 4 Place Jussieu, 75005 Paris, France.
Biocomputing Unit, Centro Nacional de Biotecnología-CSIC, Madrid 28049, Spain.
Structure. 2014 Mar 4;22(3):496-506. doi: 10.1016/j.str.2014.01.004. Epub 2014 Feb 6.
This article presents a method to study large-scale conformational changes by combining electron microscopy (EM) single-particle image analysis and normal mode analysis (NMA). It is referred to as HEMNMA, which stands for hybrid electron microscopy normal mode analysis. NMA of a reference structure (atomic-resolution structure or EM volume) is used to predict possible motions that are then confronted with EM images within an automatic iterative elastic 3D-to-2D alignment procedure to identify actual motions in the imaged samples. HEMNMA can be used to extensively analyze the conformational changes and may be used in combination with classic discrete procedures. The identified conformations allow modeling of deformation pathways compatible with the experimental data. HEMNMA was tested with synthetic and experimental data sets of E. coli 70S ribosome, DNA polymerase Pol α and B subunit complex of the eukaryotic primosome, and tomato bushy stunt virus.
本文介绍了一种通过结合电子显微镜（EM）单颗粒图像分析和简正模式分析（NMA）来研究大规模构象变化的方法。它被称为HEMNMA，即混合电子显微镜简正模式分析。参考结构（原子分辨率结构或EM体积）的NMA用于预测可能的运动，然后在自动迭代弹性3D到2D对齐程序中与EM图像进行对比，以识别成像样本中的实际运动。HEMNMA可用于广泛分析构象变化，并可与经典离散程序结合使用。所识别的构象允许对与实验数据兼容的变形途径进行建模。使用大肠杆菌70S核糖体、真核引发体的DNA聚合酶Pol α和B亚基复合物以及番茄丛矮病毒的合成和实验数据集对HEMNMA进行了测试。
