Comparing NMR and X-ray protein structure: Lindemann-like parameters and NMR disorder

Abstract

Disordered protein chains and segments are fast becoming a major pathway for our understanding of biological function, especially in more evolved species. However, the standard definition of disordered residues: the inability to constrain them in X-ray derived structures, is not easily applied to NMR derived structures. We carry out a statistical comparison between proteins whose structure was resolved using NMR and using X-ray protocols. We start by establishing a connection between these two protocols for obtaining protein structure. We find a close statistical correspondence between NMR and X-ray structures if fluctuations inherent to the NMR protocol are taken into account. Intuitively this tends to lend support to the validity of both NMR and X-ray protocols in deriving biomolecular models that correspond to in vivo conditions. We then establish Lindemann-like parameters for NMR derived structures and examine what order/disorder cutoffs for these parameters are most consistent with X-ray data and how consistent are they. Finally, we find critical value of for the best correspondence between X-ray and NMR derived order/disorder assignment, judged by maximizing the Matthews correlation, and a critical value if a balance between false positive and false negative prediction is sought. We examine a few non-conforming cases, and examine the origin of the structure derived in X-ray. This study could help in assigning meaningful disorder from NMR experiments.

Keywords:

• Lindemann parameter
• NMR
• X-ray
• Proteins in vivo

Acknowledgements

This work was supported in part by financial support provided by the National Institutes of Health (NIH) [grant number R01GM072014] and [grant number R01GM073095]. By The Research Institute at Nationwide Children’s Hospital. By the Lilly Endowment, Inc., through its support for the Indiana University Pervasive Technology Institute, by the Indiana METACyt Initiative, and by the National Science Foundation [grant number CNS-0521433], and [grant number CNS-0723054].

Notes

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported in part by The Research Institute at Nationwide Children’s Hospital, by the Lilly Endowment, Inc., through its support for the Indiana University Pervasive Technology Institute, by the Indiana METACyt Initiative, and by the National Science Foundation under [grant number CNS-0521433] and [grant number CNS-0723054]. We also gratefully acknowledge the financial support provided by the National Institutes of Health (NIH) through [grant number R01GM072014] and [grant number R01GM073095].