TY - JOUR
T1 - Sequence correction of random coil chemical shifts: correlation between neighbor correction factors and changes in the Ramachandran distribution
AU - Kjærgaard, Magnus
AU - Poulsen, Flemming Martin
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Random coil chemical shifts are necessary for secondary chemical shift analysis, which is the main NMR method for identification of secondary structure in proteins. One of the largest challenges in the determination of random coil chemical shifts is accounting for the effect of neighboring residues. The contributions from the neighboring residues are typically removed by using neighbor correction factors determined based on each residue's effect on glycine chemical shifts. Due to its unusual conformational freedom, glycine may be particularly unrepresentative for the remaining residue types. In this study, we use random coil peptides containing glutamine instead of glycine to determine the random coil chemical shifts and the neighbor correction factors. The resulting correction factors correlate to changes in the populations of the major wells in the Ramachandran plot, which demonstrates that changes in the conformational ensemble are an important source of neighbor effects in disordered proteins. Glutamine derived random coil chemical shifts and correction factors modestly improve our ability to predict (13)C chemical shifts of intrinsically disordered proteins compared to existing datasets, and may thus improve the identification of small populations of transient structure in disordered proteins.
AB - Random coil chemical shifts are necessary for secondary chemical shift analysis, which is the main NMR method for identification of secondary structure in proteins. One of the largest challenges in the determination of random coil chemical shifts is accounting for the effect of neighboring residues. The contributions from the neighboring residues are typically removed by using neighbor correction factors determined based on each residue's effect on glycine chemical shifts. Due to its unusual conformational freedom, glycine may be particularly unrepresentative for the remaining residue types. In this study, we use random coil peptides containing glutamine instead of glycine to determine the random coil chemical shifts and the neighbor correction factors. The resulting correction factors correlate to changes in the populations of the major wells in the Ramachandran plot, which demonstrates that changes in the conformational ensemble are an important source of neighbor effects in disordered proteins. Glutamine derived random coil chemical shifts and correction factors modestly improve our ability to predict (13)C chemical shifts of intrinsically disordered proteins compared to existing datasets, and may thus improve the identification of small populations of transient structure in disordered proteins.
U2 - 10.1007/s10858-011-9508-2
DO - 10.1007/s10858-011-9508-2
M3 - Journal article
C2 - 21604143
SN - 0925-2738
VL - 50
SP - 157
EP - 165
JO - Journal of Biomolecular N M R
JF - Journal of Biomolecular N M R
IS - 2
ER -