Assessment of prediction methods for protein structures determined by NMR in CASP14 : impact of AlphaFold2
Résumé
NMR studies can provide unique information about protein conformations in solution. In
CASP14, three reference structures provided by solution NMR methods were available (T1027,
T1029, and T1055), as well as a fourth data set of NMR-derived contacts for an integral
membrane protein (T1088). For the three targets with NMR-based structures, the best
prediction results ranged from very good (GDT_TS = 0.90, for T1055) to poor (GDT_TS = 0.47,
for T1029). We explored the basis of these results by comparing all CASP14 prediction models
against experimental NMR data. For T1027, NMR data reveal extensive internal dynamics,
presenting a unique challenge for protein structure prediction. The analysis of T1029 motivated
exploration of a novel method of “inverse structure determination”, in which an AF2 model was
used to guide NMR data analysis. NMR data provided to CASP predictor groups for target
T1088, a 238-residue integral membrane porin, was also used to assess several NMR-assisted
prediction methods. Most groups involved in this exercise generated similar beta-barrel models,
with good agreement with the experimental data. However, as was also observed in CASP13,
some pure prediction groups that did not use any NMR data generated models for T1088 that
better fit the NMR data than the models generated using these experimental data. These results
demonstrate the remarkable power of modern methods to predict structures of proteins with
accuracies rivaling solution NMR structures, and that it is now possible to reliably use prediction
models to guide and complement experimental NMR data analysis.
| Origine | Publication financée par une institution |
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