Improving the accuracy of macromolecular structure refinement

Authors: Brunger, A.T., Adams, P.D., Fromme, P., Fromme, R., Levitt, M., and Schröder, G.F.
Title: Improving the accuracy of macromolecular structure refinement
Source: Structure
Year: 2012
Volume: 20
Pages: 20, 957–966


In X-ray crystallography, molecular replacement and subsequent refinement is challenging at low resolution. We compared refinement methods using synchrotron diffraction data of photosystem I at 7.4 Å resolution, starting from different initial models with increasing deviations from the known high-resolution structure. Standard refinement spoiled the initial models, moving them further away from the true structure and leading to high Rfree-values. In contrast, DEN refinement improved even the most distant starting model as judged by Rfree, atomic root-mean-square differences to the true structure, significance of features not included in the initial model, and connectivity of electron density. The best protocol was DEN refinement with initial segmented rigid-body refinement. For the most distant initial model, the fraction of atoms within 2 Å of the true structure improved from 24% to 60%. We also found a significant correlation between Rfree values and the accuracy of the model, suggesting that Rfree is useful even at low resolution.

Date of online publication: Wed, 2012-06-06
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