RASP: rapid and robust backbone chemical shift assignments from protein structure

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Chemical shift prediction has an unappreciated power to guide backbone resonance assignment in cases where protein structure is known. Here we describe Resonance Assignment by chemical Shift Prediction (RASP), a method that exploits this power to derive protein backbone resonance assignments from chemical shift predictions. Robust assignments can be obtained from a minimal set of only the most sensitive triple-resonance experiments, even for spectroscopically challenging proteins. Over a test set of 154 proteins RASP assigns 88% of residues with an accuracy of 99.7%, using only information available from HNCO and HNCA spectra. Applied to experimental data from a challenging 34kDa protein, RASP assigns 90% of manually assigned residues using only 40% of the experimental data required for the manual assignment. RASP has the potential to significantly accelerate the backbone assignment process for a wide range of proteins for which structural information is available, including those for which conventional assignment strategies are not feasible.