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.
|Kim, David E; Dimaio, Frank; Yu-Ruei Wang, Ray et al. (2014) One contact for every twelve residues allows robust and accurate topology-level protein structure modeling. Proteins 82 Suppl 2:208-18|
|Demers, Jean-Philippe; Sgourakis, Nikolaos G; Gupta, Rashmi et al. (2013) The common structural architecture of Shigella flexneri and Salmonella typhimurium type three secretion needles. PLoS Pathog 9:e1003245|
|DiMaio, Frank; Zhang, Junjie; Chiu, Wah et al. (2013) Cryo-EM model validation using independent map reconstructions. Protein Sci 22:865-8|
|Song, Yifan; DiMaio, Frank; Wang, Ray Yu-Ruei et al. (2013) High-resolution comparative modeling with RosettaCM. Structure 21:1735-42|
|DiMaio, Frank; Echols, Nathaniel; Headd, Jeffrey J et al. (2013) Improved low-resolution crystallographic refinement with Phenix and Rosetta. Nat Methods 10:1102-4|
|Adams, Paul D; Baker, David; Brunger, Axel T et al. (2013) Advances, interactions, and future developments in the CNS, Phenix, and Rosetta structural biology software systems. Annu Rev Biophys 42:265-87|
|Lange, Oliver F; Baker, David (2012) Resolution-adapted recombination of structural features significantly improves sampling in restraint-guided structure calculation. Proteins 80:884-95|
|Schmitz, Christophe; Vernon, Robert; Otting, Gottfried et al. (2012) Protein structure determination from pseudocontact shifts using ROSETTA. J Mol Biol 416:668-77|
|DiMaio, Frank; Leaver-Fay, Andrew; Bradley, Phil et al. (2011) Modeling symmetric macromolecular structures in Rosetta3. PLoS One 6:e20450|
|Song, Yifan; Tyka, Michael; Leaver-Fay, Andrew et al. (2011) Structure-guided forcefield optimization. Proteins 79:1898-909|
Showing the most recent 10 out of 26 publications