Improved methodology for protein NMR structure calculation using hydrogen bond restraints and ANSURR validation: The SH2 domain of SH2B1

• Published in: Structure (London) 2023-08, Vol.31 (8), p.975-986.e3
• Main Authors: Fowler, Nicholas J., Albalwi, Marym F., Lee, Subin, Hounslow, Andrea M., Williamson, Mike P.
• Format: Article
• Language: English
• Subjects: accuracy; hydrogen bonds; NMR; protein structure; SH2B1
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2023.05.012

Protein structures calculated using NMR data are less accurate and less well-defined than they could be. Here we use the program ANSURR to show that this deficiency is at least in part due to a lack of hydrogen bond restraints. We describe a protocol to introduce hydrogen bond restraints into the structure calculation of the SH2 domain from SH2B1 in a systematic and transparent way and show that the structures generated are more accurate and better defined as a result. We also show that ANSURR can be used as a guide to know when the structure calculation is good enough to stop. [Display omitted] •We show that NMR structures typically lack hydrogen bonds•We present a protocol for gradual inclusion of hydrogen bond restraints•The resulting structures are better using many measures of quality•ANSURR provides a measure for when the NMR structure calculation is completed NMR structures of proteins need to be more accurate. Fowler et al. show that accuracy can be improved by inclusion of hydrogen bond restraints, and demonstrate an iterative method for inclusion of such restraints, showing a clear improvement in accuracy using a range of measures.