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

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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.