Tools for Generating and Assessing Pseudo-atomic Models from 3D Electron Microscopy Maps of Macromolecular Assemblies.

细胞过程由称为蛋白质和核酸的生物大分子的复杂协调和动力学控制。这些大分子不是孤立地起作用，而是形成集合体。了解这些大分子组装体的结构通常可以告诉我们它们是如何发挥作用的，这对于基本了解细胞以及开发疾病的治疗方法非常重要。结构生物学通过提供大分子组装的“图片”来帮助这个项目。这是通过使用实验技术来完成的，例如低温电子显微镜，一种将细胞成分冷冻然后用电子轰击的方法，产生样品的图像。这些图像可以结合起来，给我们一个低分辨率的组装结构的三维图片。虽然这项技术已经带来了重大发现，但由于图像分辨率低，它所能完成的工作受到限制，这给我们的知识留下了巨大的空白。我们的研究旨在通过开发计算方法来克服这一空白，该方法将各种实验来源的信息整合在一起，以构建更清晰，更完整的电子显微镜成像的组装结构图像。就像拼图游戏一样，我们将在低分辨率图片中将蛋白质的原子结构（从其他实验中已知）组合在一起，创建整个组件的精细“伪原子”图片。

Cellular processes are governed by the complex coordination and dynamics of biological macromolecules called proteins and nucleic acids. These macromolecules do not act in isolation but form assemblies. Understanding the structure of these macromolecular assemblies can often teach us how they function, which is important for the basic understanding of the cell as well as for developing cures for disease. Structural biology aids this project by providing "pictures" of macromolecular assemblies. This is done through the use of experimental techniques such as cryogenic electron microscopy, a method whereby cell components are frozen and then bombarded with electrons, yielding an image of the sample. These images can be combined to give us a low-resolution 3-dimensional picture of the assembly structure. Though this technique has led to great discoveries, there are limitations to what it can accomplish due to the low-resolution of the picture, leaving us with significant gaps in our knowledge.Our research aims to overcome this gap by developing computational methods that pull together information from a variety of experimental sources to construct clearer and more complete pictures of the assembly structures imaged by electron microscopy. Like a jigsaw puzzle, we will fit atomic structures of proteins (known from other experiments) together, within the low-resolution picture, creating a refined "pseudo-atomic" picture of the entire assembly.