冷冻电镜三维重构的关键算法研究及其应用

项目名称： 冷冻电镜三维重构的关键算法研究及其应用

项目编号： No.91530321

项目类型： 重大研究计划

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 刘红荣

作者单位： 湖南师范大学

项目金额： 350万元

中文摘要： 冷冻电镜技术具有不需要样品结晶、能解析分子量巨大的生物大分子及其复合物三维结构等优点，已发展成为结构生物学的主流技术。然而，冷冻电子显微图像的信噪比极低，且分子具有动态、复杂的三维结构，要通过二维低质图像恢复其三维结构还有许多瓶颈需要高效算法解决。本集成项目围绕重大研究计划研究目标，综合前期3个培育项目团队的优势，聚焦冷冻电镜单颗粒技术图像处理这一前沿课题开展如下研究：1）发展活性动态三维重构的新算法与软件，求解重要生物大分子动态三维结构；2）提出解决对称失配三维重构难题的新方法，求解病毒衣壳内部非二十面体对称的基因组及相关蛋白三维结构，构建病毒基因组三维折叠新模型；3）发展电子显微图像噪声抑制和颗粒全同性评估新算法，提出回答三维重构质量评估这一开放性问题的新方案；4）构建具有自主知识产权的冷冻电镜图像处理平台。本集成交叉项目的深入研究有望在冷冻电镜理论分析和应用方面取得突破性先进成果。

中文关键词： 单颗粒冷冻电镜法；动态结构；对称失配三维重构；图像处理；原子分辨

英文摘要： Cryo-electron microscopy and single-particle three-dimensional (3D) reconstruction technique (commonly referred to collectively as cryo-EM) has become one of the most powerful tools for structural biology, because the biological samples need not to be crystallized and can be kept in their native environment, and the structures of macromolecules and macromolecular complexes can be resolved to near-atomic resolution by this tool. However, there are still some problems on restoring the whole atomic structures of macromolecules from two-dimensional images due to its extremely low signal-to-noise ratio and the dynamic processes of biological macromolecules. Based on the goals of this major research plan and the advantages of our previous three projects, we focus on the image process of cryo-EM, and propose this integrated project. The goals of our project are to: 1) propose the new methods on dynamic reconstruction and resolve the dynamic structures of macromolecules; 2) propose the new methods on symmetry-mismatch 3D reconstruction, and use this methods to resolve the non-icosahedral symmetry structures within the icosahedral capsid of virus, and build the 3D models of viral genome; 3) develop the efficient theory and algorithms for noise suppression, particle heterogeneity, density maps validation to push the 3D reconstruction of cryo-EM to atomic resolution; 4) design a high-precision and large-scale data processing platform for cryo-EM data-process. We expect to achieve breakthrough in the field of cryo-EM by this multi-discipline research.

英文关键词： cryo-EM single particle;dynamical structure;symmetry-mismatch reconstruction;image processing;atomic resolution