论文标题

原子结构的光谱分解在异质性冷冻EM中

Spectral decomposition of atomic structures in heterogeneous cryo-EM

论文作者

Esteve-Yagüe, Carlos, Diepeveen, Willem, Öktem, Ozan, Schönlieb, Carola-Bibiane

论文摘要

我们考虑了从异质性冷冻EM数据集中恢复柔性大分子的三维原子结构的问题。该数据集包含大分子静电电位的嘈杂层析成像投影,从不同的观察方向采取,在异质情况下,每个图像对应于大分子的不同构象。在假设大分子可以建模为链或离散曲线的假设(例如,它是具有单个氨基酸链链的蛋白质主链的情况),我们引入了一种方法,以估算与给定构型相对于先验构型的原子模型变形的方法,这是众所周知的。我们的方法包括在每种构象中估算原子模型的扭转和键角,作为在构象的歧管中,拉普拉斯操作员特征函数的线性组合。这些本征函数可以通过使用Cryo-EM数据集的图形laplacian的构建,可以通过多种学习中的知名技术近似。最后,我们使用合成数据集测试我们的方法,从嘈杂的层析图投影中恢复了二维和三维柔性结构的原子模型。

We consider the problem of recovering the three-dimensional atomic structure of a flexible macromolecule from a heterogeneous cryo-EM dataset. The dataset contains noisy tomographic projections of the electrostatic potential of the macromolecule, taken from different viewing directions, and in the heterogeneous case, each image corresponds to a different conformation of the macromolecule. Under the assumption that the macromolecule can be modelled as a chain, or discrete curve (as it is for instance the case for a protein backbone with a single chain of amino-acids), we introduce a method to estimate the deformation of the atomic model with respect to a given conformation, which is assumed to be known a priori. Our method consists on estimating the torsion and bond angles of the atomic model in each conformation as a linear combination of the eigenfunctions of the Laplace operator in the manifold of conformations. These eigenfunctions can be approximated by means of a well-known technique in manifold learning, based on the construction of a graph Laplacian using the cryo-EM dataset. Finally, we test our approach with synthetic datasets, for which we recover the atomic model of two-dimensional and three-dimensional flexible structures from noisy tomographic projections.

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