Assessing precision and accuracy of protein structures derived from NMR data

One of the most challenging problems facing the field of biomolecular NMR spectroscopy is the lack of generally accepted, uniform criteria for defining the precision and accuracy of structures derived from NMR data. Although widely cited, metrics such as residual constraint violations, constraints per residue, and convergence across an ensemble of conformers [root-mean-square deviations (RMSDs)] provide necessary, but not sufficient, criteria for defining a good-quality solution NMR structure. Most importantly, none of these measures have standard conventions by which they are computed; each measure is assessed somewhat differently in different laboratories, using subjective criteria which may not be possible to reproduce in another laboratory. Owing to the lack of widely accepted algorithms and conventions for making these assessments, the same structure analyzed by different groups will often yield different structure quality assessment statistics. Two articles in this issue of Proteins demonstrate the pressing need for establishing community-wide standards for defining the accuracy and precision of NMR-derived protein structures. In one article, Snyder and Montelione present a method for determining internally well-defined “core atom set(s)” based on distance variance matrices, and for calculating a “joint RMSD” quantifying the precision of an ensemble of NMR-derived structures. In the other article, Nederveen et al. recalculate over 500 NMR-derived structures from archived constraint files, and demonstrate the value of standardized methods of structure calculation and assessment. They show that not only can improved methods of structure calculation provide more accurate results, but also that the original published structures often are reported with an inappropriately high estimation of precision. Both of these articles address key aspects of the challenge for assessing the precision and accuracy of protein structures derived from NMR data. This editorial addresses the general issues of estimating precision and accuracy of protein NMR structures, and presents recent progress in the field, with the aim of stimulating discussion, and eventually resolution, of these challenges by the scientific community.