Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta
Cryo-EM has revealed the structures of many challenging yet exciting macromolecular assemblies at near-atomic resolution (3-4.5Å), providing biological phenomena with molecular descriptions. However, at these resolutions accurately positioning individual atoms remains challenging and error-prone. Manually refining thousands of amino acids - typical in a macromolecular assembly - is tedious and time-consuming. We present an automated method that can improve the atomic details in models manually built in near-atomic-resolution cryo-EM maps. Applying the method to three systems recently solved by cryo-EM, we are able to improve model geometry while maintaining the fit-to-density. Backbone placement errors are automatically detected and corrected, and the refinement shows a large radius of convergence. The results demonstrate the method is amenable to structures with symmetry, of very large size, and containing RNA as well as covalently bound ligands. The method should streamline the cryo-EM structure determination process, providing accurate and unbiased atomic structure interpretation of such maps.
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The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Axel T Brunger, Howard Hughes Medical Institute, Stanford University, United States
- Received: April 26, 2016
- Accepted: September 22, 2016
- Accepted Manuscript published: September 26, 2016 (version 1)
- Version of Record published: November 18, 2016 (version 2)
© 2016, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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