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Prevention of overfitting in cryo-EM structure determination

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Figure 1: The prevention of overfitting.


  1. Henderson, R. et al. Structure 20, 205–214 (2012).

    CAS  Article  Google Scholar 

  2. Saxton, W.O. & Baumeister, W. J. Microsc. 127, 127–138 (1982).

    CAS  Article  Google Scholar 

  3. Stewart, A. & Grigorieff, N. Ultramicroscopy 102, 67–84 (2004).

    CAS  Article  Google Scholar 

  4. Scheres, S.H. J. Mol. Biol. 415, 406–418 (2012).

    CAS  Article  Google Scholar 

  5. Henderson, R. et al. J. Mol. Biol. 413, 1028–1046 (2011).

    CAS  Article  Google Scholar 

  6. Scheres, S.H. et al. Nat. Protoc. 3, 977–990 (2008).

    CAS  Article  Google Scholar 

  7. Böttcher, B., Wynne, S.A. & Crowther, R.A. Nature 386, 88–91 (1997).

    Article  Google Scholar 

  8. Rosenthal, P.B. & Henderson, R. J. Mol. Biol. 333, 721–745 (2003).

    CAS  Article  Google Scholar 

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We are grateful to T. Crowther and R. Henderson for helpful discussions and to J. Grimmett for help with computing. T. Crowther provided hepatitis B data, and the National Center for Macromolecular Imaging, which is funded by US National Institutes of Health grant P41RR02250, provided GroEL data. This work was funded by the UK Medical Research Council through grant MC_UP_A025_1013 to S.H.W.S.

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Correspondence to Sjors H W Scheres.

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Supplementary Figures 1–4, Supplementary Table 1, Supplementary Methods and Supplementary Software (PDF 765 kb)

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Scheres, S., Chen, S. Prevention of overfitting in cryo-EM structure determination. Nat Methods 9, 853–854 (2012).

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