A major current focus of modern structural biology is the determination of the structures of macromolecular assemblies and machines. Such systems are often not amenable to high-resolution x-ray crystallographic techniques. This proposal aims to develop powerful new methods which integrate NMR data, information from homologous structures, cryo electron microscopy data, low resolution x-ray crystallographic data, evolutionary covariance data, and other sources of information to generate models with atomic level accuracy for macromolecular assemblies and machines. With collaborators, the new methodology will be used to solve cutting-edge structural biology problems which cannot be solved by currently available methods. The new methodology will be incorporated into the freely available Rosetta software suite for use throughout the scientific community.
Proteins are the workhorses of living things. The structures of proteins are critical to carrying out their functions. This research will contribute to determining the structures of protein assemblies critical to life and human disease.
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