Accurate Random Coil Chemical Shifts from an Analysis of Loop Regions in Native States of Proteins

The definition of a standard set of reference random coil chemical shift values is a key component in many applications of protein NMR spectroscopy.1-3 The comparison of measured chemical shifts with their random coil counterparts is commonly used to identify secondary structure elements in folded proteins and to reveal the presence of regions with residual structure in unfolded states.3,4 The importance of measuring backbone chemical shifts in unfolded states has recently been further increased with the recognition that proteins containing natively unfolded regions may represent up to one-third of eukaryotic proteomes and play a variety of essential biological roles;5 furthermore, it has also been realized that several amyloidogenic proteins associated with neurodegenerative diseases are natively unfolded.6 Several methods have been proposed for associating random coil chemical shift values to amino acid sequences of proteins base