New methods for low-resolution crystallographic refinement

While determination of X-ray crystal structures at moderate to high resolutions has recently accelerated, structure determination and refinement at lower resolutions remains problematic despite considerable recent work. By combining combining the strengths of the Rosetta structure modeling methodology and the Phenix X-ray refinement software, we see significant improvements in refinement at low resolution.

Validating protein structures fit into cryoEM density maps

Increasingly, cryo-electron microscopy reconstructions are of suitable resolution to permit tracing protein backbones and identify sidechain conformations. For evaluating atomic models constructed and refined into such maps, it is critical to have some validation metric for assessing the fit of the models to the data. Such a metric would provide a means to determine the proper balance between the fit to the density and model energy and stereochemistry during refinement, and is likely to be useful in determining values of model building and refinement metaparameters quite generally.

Increasing the radius of convergence of molecular replacement by density- and energy-guided optimization

The crystallographic phase problem refers to the fact that when X-ray diffraction data is collected, additional data -- the "phases" -- are needed to construct a map of the protein's density. Molecular replacement (MR) is a method in which a previously solved protein structure (the "template") is used to fill in this missing experimental information for a target protein. The method generally works, assuming template and target are reasonably similar. However, when the template and target have less than 30% sequence identity, molecular replacement often will fail.

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