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Improved low-resolution crystallographic refinement with Phenix and Rosetta

Nature Methods volume 10, pages 1102–1104 (2013)Cite this article

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Abstract

Refinement of macromolecular structures against low-resolution crystallographic data is limited by the ability of current methods to converge on a structure with realistic geometry. We developed a low-resolution crystallographic refinement method that combines the Rosetta sampling methodology and energy function with reciprocal-space X-ray refinement in Phenix. On a set of difficult low-resolution cases, the method yielded improved model geometry and lower free R factors than alternate refinement methods.

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Figure 1: Comparison of Phenix, CNS-DEN, REFMAC5 and Rosetta-Phenix refinements on a realistic low-resolution test set of 15 proteins (Supplementary Table 1).
Figure 2: Refinement of the Ca2+ ATPase (PDB 3FPS, PDB 2ZBG) using Rosetta-Phenix.

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Acknowledgements

We thank P. Afonine and R. Grosse-Kunstleve for technical advice, J. Richardson for the HiQ54 test structures, and P. Afonine, J. Fraser, R. Read and J. Richardson for comments on the manuscript. Funding was provided by the US National Institutes of Health (grant nos. GM063210 and GM092802). This work was supported in part by the US Department of Energy under contract no. DE-AC02-05CH11231.

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Author notes

  1. Frank DiMaio and Nathaniel Echols: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, University of Washington, Seattle, Washington, USA

    Frank DiMaio & David Baker

  2. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA

    Nathaniel Echols, Jeffrey J Headd & Paul D Adams

  3. Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA

    Thomas C Terwilliger

  4. Department of Bioengineering, University of California Berkeley, Berkeley, California, USA

    Paul D Adams

  5. Howard Hughes Medical Institute, University of Washington, Seattle, USA

    David Baker

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  1. Frank DiMaio
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  4. Thomas C Terwilliger
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  5. Paul D Adams
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Contributions

F.D., N.E., T.C.T., P.D.A. and D.B. designed the research; F.D., N.E. and J.J.H. performed the experiments; F.D. and N.E. wrote the manuscript, and all authors edited and read the final manuscript; P.D.A. and D.B. supervised the project.

Corresponding authors

Correspondence to Frank DiMaio or Nathaniel Echols.

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The authors declare no competing financial interests.

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Supplementary Figures 1–6 and Supplementary Tables 1–5 (PDF 993 kb)

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DiMaio, F., Echols, N., Headd, J. et al. Improved low-resolution crystallographic refinement with Phenix and Rosetta. Nat Methods 10, 1102–1104 (2013). https://doi.org/10.1038/nmeth.2648

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