The application of 1H NMR chemical shift calculations to diastereotopic groups in proteins

We have calculated chemical shifts for a range of diastereotopic protons in proteins (i.e. methylene protons, and the methyl groups of valine and leucine residues), using a recently optimised method for chemical shift calculation. The calculations are based on crystal structure coordinates, and ave been compared with experimental stereospecific assignments. The results indicate that chemical shifts can be used to suggest stereospecific assignments with about 80% probability of being correct, in cases where both the experimental and the calculated chemical shift differences between a pair of diastereotopic protons are greater than 0.3 ppm. Inaccurate calculations are shown to be caused in most cases by differences between crystal and solution structures. Furthermore, chemical shift calculations based on NMR structures are shown to be capable of acting as a further constraint on structure, by limiting the range of side‐chain conformations adopted in structures calculated from NMR data.

[1]  K Wüthrich,et al.  Determination of the complete three-dimensional structure of the alpha-amylase inhibitor tendamistat in aqueous solution by nuclear magnetic resonance and distance geometry. , 1988, Journal of molecular biology.

[2]  G. Wagner NMR INVESTIGATIONS OF PROTEIN STRUCTURE , 1990 .

[3]  M. Williamson,et al.  Calculation of chemical shifts of protons on alpha carbons in proteins , 1991 .

[4]  K. Wüthrich,et al.  1H And 13C NMR chemical shifts of the diastereotopic methyl groups of valyl and leucyl residues in peptides and proteins , 1990 .

[5]  S. Hyberts,et al.  Stereospecific assignments of side-chain protons and characterization of torsion angles in Eglin c. , 1987, European journal of biochemistry.

[6]  Timothy F. Havel An evaluation of computational strategies for use in the determination of protein structure from distance constraints obtained by nuclear magnetic resonance. , 1991, Progress in biophysics and molecular biology.

[7]  J Otlewski,et al.  Determination of the complete three-dimensional structure of the trypsin inhibitor from squash seeds in aqueous solution by nuclear magnetic resonance and a combination of distance geometry and dynamical simulated annealing. , 1989, Journal of molecular biology.

[8]  F. Richards,et al.  NMR sequential assignment of Escherichia coli thioredoxin utilizing random fractional deuteriation. , 1988, Biochemistry.

[9]  M. Williamson,et al.  A method for the calculation of protein α-CH chemical shifts , 1992 .

[10]  C. Dobson,et al.  Analysis of phi and chi 1 torsion angles for hen lysozyme in solution from 1H NMR spin-spin coupling constants. , 1991, Biochemistry.