The accuracy of protein structures in solution determined by AlphaFold and NMR

In the recent Critical Assessment of Structure Prediction (CASP) competition, AlphaFold2 performed outstandingly. Its worst predictions were for nuclear magnetic resonance (NMR) structures, which has two alternative explanations: either the NMR structures were poor, implying that Alpha-Fold may be more accurate than NMR, or there is a genuine difference between crystal and solution structures. Here, we use the program Accuracy of NMR Structures Using RCI and Rigidity (ANSURR), which measures the accuracy of solution structures, and show that one of the NMR structures was indeed poor. We then compare Alpha-Fold predictions to NMR structures and show that Alpha-Fold tends to be more accurate than NMR ensembles. There are, however, some cases where the NMR ensembles are more accurate. These tend to be dynamic structures, where Alpha-Fold had low confidence. We suggest that Alpha-Fold could be used as the model for NMR-structure refinements and that Alpha-Fold structures validated by ANSURR may require no further refinement. [Display omitted] •We survey 904 human proteins with both Alpha-Fold and NMR structures•Alpha-Fold predictions are usually more accurate than NMR structures•NMR can be better than Alpha-Fold where there are local dynamics•NMR is useful to validate Alpha-Fold predictions and refine where necessary Fowler and Williamson compared AlphaFold2 and NMR structures for 904 human proteins. The best NMR structures in each ensemble are of comparable accuracy to AlphaFold2 (AF2). In 30% of cases, AF2 is significantly better, mainly in hydrogen-bond networks; in 2% of cases, NMR is better, mainly in dynamic regions.