Amino Acids, Peptides and 2 EMPIRICAL SURVEYS OF CHEMICAL SHIFTS IN

PEPTIDES AND PROTEINS

Proteins: Chemical Shifts
David A. Case 2.1 Peptides
The Scripps Research Institute, La Jolla, CA, USA
Short, unstructured peptides provide a useful reference point
for many examinations of protein shifts, since they embody
most of the local contributions that depend upon the chemical
1 Introduction 1 nature of the amino acid side chain, but lack the longer range
2 Empirical Surveys of Chemical Shifts in Peptides and contributions characteristic of folded proteins. The values most
Proteins 1 often cited are those of Bundi and Wüthrich (for protons),4 and
3 Chemical Shifts and Secondary Structure 2 Richarz and Wüthrich (for 13 C),5 based on the peptide H-Gly-
4 Chemical Shifts and Tertiary Structure 3 Gly-X-Ala-OH, where X represents any of the 20 common
5 Conclusions 4 amino acids. Table 1 lists these values for the backbone
6 Related Articles 4 nuclei. It is common practice to define a ‘structural’ shift
7 References 4 as the difference between an observed resonance position
in a protein or structured peptide and these ‘random coil’
values.
In principle, peptide shifts like these could be computed
from first principles using quantum chemistry calculations.
At present such calculations are limited to relatively small
1 INTRODUCTION molecules in the gas phase, and are generally not of routine
‘chemical’ accuracy, at least when one is considering nuclei
Perhaps the most direct observables in NMR spectra are in different bonding environments.6 The situation is changing
the positions of the resonances, which are generally reported rapidly, however, and ab initio calculations with reasonable
as chemical shifts relative to a standard position. The very basis sets are now feasible for protein fragments such as amino
existence of useful spectra depends upon chemical shift acids and dipeptides.7 – 11 Such calculations appear to be able
dispersion, so that nuclei in chemically distinct positions to rationalize the dependence of some shifts on backbone
resonate at different frequencies. For peptides and proteins it is dihedral angles, and point the way to the exploration of
convenient to divide the origins of chemical shift differences other effects such as hydrogen bonding and external electric
into two components: the first arises from variations in the fields. Because a variety of effects are important in influencing
local electronic environment, so that aromatic and aliphatic shifts, reliable computational studies on amino acids and
protons, for example, have characteristic shifts that differ from peptides could have an important impact in the next few
each other and from amide protons. A second component years.
of chemical shift dispersion occurs with nominally identical
protons, such as valine Hα, due to variations in the nature of 2.2 Proteins
adjoining residues and especially to conformational differences
in secondary and tertiary structure. While there is no sharp The primary empirical study of chemical shifts in proteins
distinction between these two components, the ‘local’ effects is that of Wishart et al.12 who correlated observed chemical
usually arise from variations in shielding by electrons in the shifts and secondary-structure assignments in over 70 proteins,
bonds that contain (or are adjacent to) the resonating nucleus, and computed averages and distributions for shifts in helix,
whereas the longer range effects are generally ‘through-space’ β-strand, and coil configurations. Table 1 gives the results
interactions involving functional groups separated by many (not sorted by secondary structure) for a larger sample drawn
chemical bonds from the nucleus in question. from the BioMagResBank database.3 There are only minor
This article surveys both empirical trends and theoretical differences between the proton averages given in Table 1 and
approaches to understanding chemical shift trends in amino the earlier results; for the amide 15 N shifts, results for M, P and
acids, peptides and proteins. The main emphasis is on T differ by more than 1 ppm between the two compilations;
connections between conformation (especially secondary and for 13 Cα, C, M, N, Q and W differ by at least 1 ppm; the
tertiary structure) and chemical shift. It has been clear for some majority of values for the carbonyl 13 C shift differ by at least
time that chemical shifts in proteins and peptides depend upon this much, perhaps reflecting the small number of available
structure in a reasonably regular way, so that, for example, shifts even now. As might be expected, the Cα and Hα nuclei,
the shifts in structurally homologous proteins are themselves which are closest to the side chain, show a strong correlation
homologous.1,2 One force driving recent reexaminations of the between the median shift observed in proteins and the ‘random
origins of chemical shift dispersion has been the rapid growth coil’ peptide value: linear correlation coefficients are 0.95 and
in the number of protein and peptide assignments. Many of 0.99 for Hα and Cα respectively. On the other hand, median
these are now available in a relational database that contains shifts in proteins for the amide proton and carbonyl carbon
about 140 000 assignments.3 While much of the ‘information are only weakly related to the peptide random coil shifts,
content’ of these data remains to be discovered, the following with correlation coefficients of 0.11, and 0.56, respectively.
two sections outline some of the clear trends that emerge from This suggests that longer range interactions, such as hydrogen
surveys of shift distributions bonding, may be important in influencing these shifts.

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This article is © 2007 John Wiley & Sons, Ltd.
This article was previously published in the Encyclopedia of Magnetic Resonance in 2007 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470034590.emrstm0008
2 AMINO ACIDS, PEPTIDES & PROTEINS: CHEMICAL SHIFTS

Table 1 Backbone Shift Distributions in proteina

HN Hα
Res. No. Median SD rc No. Median SD rc
A 1446 8.16 0.61 8.25 1429 4.18 0.50 4.35
C 882 8.44 0.66 8.31 942 4.72 0.63 4.69
D 975 8.34 0.62 8.41 936 4.59 0.32 4.76
E 1225 8.30 0.68 8.37 1167 4.17 0.45 4.29
F 668 8.40 0.76 8.23 694 4.61 0.61 4.66
G 1485 8.33 1.31 8.39 2295 3.92 0.68 3.97
H 421 8.27 0.96 8.41 450 4.61 1.02 4.63
I 789 8.24 0.68 8.19 807 4.15 0.62 4.23
K 1593 8.17 0.75 8.41 1500 4.20 0.48 4.36
L 1447 8.19 0.73 8.42 1426 4.24 0.51 4.38
M 326 8.30 0.63 8.42 325 4.29 0.49 4.52
N 862 8.33 0.84 8.42 827 4.67 0.46 4.75
P – – – – 683 4.42 0.40 4.44
Q 730 8.16 0.65 8.41 683 4.25 0.46 4.37
R 892 8.23 0.58 8.27 848 4.25 0.46 4.38
S 1113 8.27 1.43 8.38 1118 4.45 0.44 4.50
T 1082 8.16 0.82 8.24 1087 4.40 0.57 4.35
V 1157 8.21 0.82 8.44 1202 4.08 0.86 4.18
W 227 8.26 0.86 8.09 220 4.63 0.61 4.70
Y 685 8.26 0.81 8.18 717 4.58 0.61 4.60

N Cα C
Res. No. Median SD No. Median SD rc No. Median SD rc
A 335 122.8 8.7 118 52.1 2.1 50.8 40 177.8 2.4 175.8
C 62 117.8 3.7 35 55.0 3.1 53.9 40 172.2 2.0 173.9
D 216 120.3 4.1 77 53.0 2.1 52.7 31 176.9 1.4 174.2
E 258 120.9 3.2 112 56.7 2.6 55.4 42 177.2 2.1 173.7
F 136 121.3 4.4 79 56.2 2.6 56.2 38 174.7 2.5 172.9
G 277 109.1 4.0 171 44.0 1.9 43.9 52 172.7 2.1 171.8
H 59 119.5 3.5 30 53.8 5.7 53.6 6 175.8 1.8 172.2
I 169 123.6 4.6 59 60.0 3.0 59.6 22 175.8 1.9 174.2
K 364 120.7 4.0 153 56.0 2.1 54.6 30 175.7 2.2 174.5
L 289 122.0 4.4 115 53.7 1.9 53.8 26 176.5 1.8 174.7
M 79 120.9 4.8 42 54.7 2.2 54.0 19 177.4 1.8 173.4
N 172 118.9 5.1 65 52.7 1.9 53.8 26 173.7 1.9 173.1
P 34 137.7 3.8 61 62.3 1.6 61.9 19 175.0 2.1 174.1
Q 179 120.2 3.8 64 55.4 2.1 54.1 19 175.1 1.8 174.0
R 128 120.7 3.7 57 55.6 2.5 54.6 31 174.7 3.7 173.4
S 166 116.9 3.6 78 57.0 1.9 56.6 19 173.7 1.6 172.6
T 200 115.7 5.6 111 60.3 2.6 60.1 38 174.8 1.9 172.5
V 237 121.3 6.0 92 60.8 2.9 60.7 24 174.8 2.1 173.9
W 41 120.3 4.0 16 55.7 2.2 55.7 0 – – 173.4
Y 114 121.2 5.5 69 55.7 1.7 56.3 14 173.9 1.9 172.9

a Data extracted from version 1.0 of the BioMagResBank database.3 For each shift, the first three columns list the number of shifts, the median
value and the standard deviation SD about the mean Column labeled ‘rc’ gives peptide shifts for H-Gly-Gly-X-Ala-OH from Bundi and Wüthrich4
and Richarz and Wüthrich.5

3 CHEMICAL SHIFTS AND SECONDARY The same general trend is found for amide protons, whereas
STRUCTURE Hβ shifts move in the opposite direction by a smaller amount.
Amide protons at the N-terminus of helices tend to be shifted
Considerable attention has been paid to ways in which to high frequency compared with those at the C-terminus.
the Hα shift reflects local secondary structure. It has been These relationships are in many cases clear enough to drive
recognized for some time that β-sheet regions show high- secondary-structure assignments in proteins,13,14 and to gain
frequency shifts for this resonance, while helical regions show a qualitative idea of structural differences among homologous
low-frequency shifts. In the Wishart et al.12 survey, the mean systems. It has been shown that this dependence of Hα and
Hα positions in helices and sheets differ by nearly 0.8 ppm, and Hβ shifts on secondary structure can be explained in terms of
there is remarkably little overlap between the two distributions. peptide group contributions, as outlined below.15

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This article is © 2007 John Wiley & Sons, Ltd.
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DOI: 10.1002/9780470034590.emrstm0008
 AMINO ACIDS, PEPTIDES & PROTEINS: CHEMICAL SHIFTS 3

These ideas may also be of use for linear peptides, where is conventional to incorporate in B those constants that would
conformational heterogeneity hampers quantitative NOE-based yield the expected contribution from a benzene ring, and to use
structure calculations. For example, amide proton shifts in i # (the ‘ring current intensity’ factor) to represent the ratio
model helical peptides are often periodic (with a 3–4 residue of the intensity expected for the ring in question to that of
repeat pattern);16,17 amphipathic helices show a periodic a benzene ring. There have been several attempts to estimate
behavior that appears to be related to curving of the helix these factors, based on both quantum mechanical and empirical
axis;18,19 and it may be possible to characterize helices calculations37,38
of marginal stability through an analysis of the solvent Two commonly used parameterizations of the geometric
dependence of backbone shifts.20 factors were proposed by Johnson and Bovey39 and by Haigh
The relationship of 15 N and 13 C shifts to secondary structure and Mallion.34 In the latter model, which is one of the simplest
is also of considerable current interest.9 – 12,21 Cα and carbonyl to implement, the geometric factor is
shifts exhibit a strong correlation with secondary structure,  
both moving to higher frequency in helical conformations and
1 1
to lower frequency in β-strand or extended configurations. G(r) = sij + 3 (1)
As with Hα shifts, there is surprisingly little overlap between ij
ri3 rj
the distributions, which suggests that reliable conformational
conclusions may be drawn, and the Cα shift has been Here r i and r j are the distances from ring atoms i and j to the
used as a site-specific probe of the helix/coil transition in proton, and s ij is the area of the triangle formed by atoms i and
linear peptides.22 There are also indications from solid state j and the proton projected onto the plane of the aromatic ring.
studies of peptides that the carbonyl 13 C resonance moves to The sum is over the bonds in the ring. The Johnson–Bovey
higher frequency with decreasing CO· · · HN hydrogen-bond model sets up ‘rings’ of current above and below the plane of
length,23 – 27 a result that is in rough accord with quantum the atoms, and computes fields from this model. There appears
chemical calculations.26 Cβ shifts also show systematic to be very little difference between the two models, except at
differences between helices and sheets, but with much more very short distances.
overlap in the observed distributions. The heme group is an important special case for ring
The situation for amide 15 N shifts in proteins (as with amide current calculations, and a variety of empirical calculations
protons) is less clear. There are general differences between have been carried out.40 – 43 A simple model that gives good
shifts in helix and sheet structures of about 3 ppm, but the results treats the heme as five rings: four for the pyrroles,
overlap between the two distributions is often greater than and one ‘macrocycle’ that traverses the large conjugated ring
this, so that it is difficult to draw simple conclusions from a in the canonical valence-bond structure. Cross and Wright43
given set of shifts.12,28,29 There is a correlation between amide compared the results of this and other models with a dataset
proton and amide 15 N shifts, suggesting that similar physical composed of protein and model compound shifts, and Ösapay
effects are influencing both. There is some evidence that 15 N and Case38 used a larger heme protein database, including
shifts may be periodic in helices, reflecting the local structure, cytochromes c, b 5 , and c 551 and myoglobin. The empirical
but the relationship does not appear to be a simple one.16,30 formulas appear to reproduce the observed behavior quite well.

4 CHEMICAL SHIFTS AND TERTIARY STRUCTURE 4.2 Peptide Group Contributions

In both organic chemistry and biochemistry, empirical It has been recognized for some time that the magnetic
analyses of the effects of ‘distant’ substituents on chemical anisotropy of the peptide group is likely to contribute
shifts have played an important role for many years.31 There significantly to chemical shifts in proteins. McConnell35 has
are generally two such types of interaction: magnetic fields shown that when the observed proton and the ‘source’ of the
arising from anisotropies in the magnetic susceptibilities of magnetic anisotropy are far apart, the contribution to the local
distant functional groups, and electric fields created by distant shielding tensor depends upon the magnetic anisotropy of the
dipoles or charges. The former are strongest with conjugated distant group:
or partially delocalized electrons (such as in aromatic rings

or peptide groups) where there are significant anisotropies σm = (3L0 R 3 )−1 χii (1 − 3 cos2 θi ) (2)
in group magnetic susceptibilities.32 – 34 These groups then i=x,y,z
respond to an external spectrometer field B0 to create a
local magnetic field which can augment or oppose B0 .35 The Here L0 is the Avogadro constant, R is the distance from
electrostatic fields of distant groups influence chemical shifts the proton to the distant group, χ ii is a component of the
indirectly, by polarizing chemical bonds, and thus contributing magnetic susceptibility tensor, and θ i is the angle between
to shielding or deshielding of the nuclei.36 These mechanisms the i axis and the radius vector R. Since there is no direct
are considered in more detail in the following paragraphs. method for measuring the magnetic anisotropy of a peptide
group within a protein, all estimates of these effects are to
some extent empirical. Data for formamide44 suggest that the
4.1 Ring Current Calculations peptide group is nearly axially symmetric about the out-of-
plane axis, with an anisotropy χ of −5.1 ± 0.6 × 10−6
The general form of empirical theories is σ rc = iBG(r) where erg (G2 -mol)−1 . This value is in good agreement with the one
r is the vector from the observed proton to the aromatic ring, obtained using an empirical theoretical approach developed by
G(r) is a geometric factor, and i and B are constants.31,34 It Pauling:33 5.4 10−6 erg (G2 -mol)−1 .

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This article was previously published in the Encyclopedia of Magnetic Resonance in 2007 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470034590.emrstm0008
4 AMINO ACIDS, PEPTIDES & PROTEINS: CHEMICAL SHIFTS

Alternative models for peptide groups can be constructed by 5 CONCLUSIONS

adding contributions from individual atoms45 or bonds,46 – 48
rather than using parameters for the peptide group as a whole. There is little doubt that the use of chemical shift information
These alternative methods give generally similar results.49,50 for peptides and proteins will continue to grow as a source
Contributions from peptide groups calculated in this way of structural information. The Hα and Cα shifts appear to
can explain to a large extent the observed behavior of Hα provide a reliable indicator of local secondary structure, and
chemical shifts as a function of local secondary structure.15 useful theories are available for magnetic interactions with
Because of the R −3 distance dependence in equation (2), the aromatic rings and peptide groups. Electrostatic interactions
neighboring peptide groups have the greatest influence, so that (including hydrogen bonding and solvation effects) are less
the shift depends to a large extent on the backbone dihedral well understood. Ab initio electronic structure calculations
angles φ and ψ, which determine the geometric relationship are beginning to address problems of interest to peptide and
between the peptide planes and the Hα position. protein chemists, and this, together with empirical analyses of
larger numbers of shifts, should provide new insight into the
origins of chemical shift dispersion.
4.3 Electrostatic Contributions

A significant contribution to chemical shifts can also arise

from distant charges and dipoles, which can polarize the C–H 6 RELATED ARTICLES
bond and thereby increase or decrease the local shielding
by electrons. The most significant term is expected to be Carbon-13 Spectral Simulation; Shielding Calculations:
proportional to the projection of the local electric field onto LORG and SOLO Approaches; Chemical Shifts in Biochem-
the C–H vector: ical Systems; Shielding: Overview of Theoretical Methods;
Shielding in Small Molecules.
σel = AE(C–H) (3)

Buckingham36 suggested that an appropriate value for A

would be −2 × 10−12 esu−1 , but this magnitude clearly 7 REFERENCES
depends upon the way in which local electric fields are
estimated. Most estimates to date have been based on 1. C. Redfield and J. P. Robertson, in Computational Aspects of the
Coulomb’s law using partial charge models from molecular Study of Biological Macromolecules by NMR Spectroscopy, ed. J.
mechanics force fields, but this approach ignores important Hoch, F. M. Poulsen, and C. Redfield, Plenum, New York, 1991,
solvent effects that screen charge interactions, and further work pp. 303–316.
in this area is needed. 2. B. J. Stockman, T. A. Scahill, N. A. Strakalaitis, D. P. Brunner,
The relative importance of various contributions is expected A. W. Yem, and M. R. Deibel, Jr., J. Biomol. NMR, 1992, 2,
to be different for protons than for heavier nuclei. Ring current 591.
and magnetic anisotropy contributions will contribute the same 3. B. R. Seavey, E. A. Farr, W. M. Westler, and J. L. Markley, J.
absolute shift for all nuclei, and hence should be less important Biomol. NMR, 1991, 1, 217.
for nuclei like 13 C or 15 N that have large chemical shift 4. A. Bundi and K. Wüthrich, Biopolymers, 1979, 18, 285.
ranges (compared with protons). These heavier nuclei, on the 5. R. Richarz and K. Wüthrich, Biopolymers, 1978, 17, 2133.
other hand, are more sensitive to electrostatic effects than are 6. G. A. Webb, in Nuclear Magnetic Shieldings and Molecular
protons, probably because of the ability of electric fields to Structure, ed. J. A. Tossell, Kluwer, Dordrecht, 1993, pp. 1–25.
polarize their occupied p shells, which are unoccupied for 7. D. B. Chestnut and C. G. Phung, Chem. Phys. Lett., 1991, 183,
hydrogen,51 and some interesting attempts have been made to 505.
correlate shifts in proteins with estimates of the local electric 8. D. B. Chestnut and C. G. Phung, in Nuclear Magnetic Shieldings
fields.52,53 and Molecular Structure, ed. J. A. Tossell, Kluwer, Dordrecht,
The analysis of chemical shift patterns using these ideas 1993, pp. 221–241.
has a long history in organic chemistry.31,34,46 Recently, 9. D. Jiao, M. Barfield, and V. J. Hruby, J. Am. Chem. Soc., 1993,
several groups have shown that such calculations can explain 115, 10883.
a large portion of the chemical shift dispersion seen in 10. A. C. de Dios, J. G. Pearson, and E. Oldfield, J. Am. Chem. Soc.,
globular proteins.38,47,48,54,55 For example, Ösapay and 1993, 115, 9768.
Case38 analyzed proton shifts from 17 proteins whose X- 11. A. C. de Dios, J. G. Pearson, and E. Oldfield, Science, 1993, 260,
ray crystal structures had been determined; for 5678 protons 1491.
bonded to carbon they obtained a linear correlation coefficient 12. D. S. Wishart, B. D. Sykes, and F. M. Richards, J. Mol. Biol.,
of 0.88 between the calculated and observed structural shifts, 1991, 222, 311.
with an rms error of 0.23 ppm; for side-chain protons in 13. D. S. Wishart, B. D. Sykes, and F. M. Richards, Biochemistry,
nonheme proteins the rms error was 0.18 ppm, and for methyl 1992, 31, 1647.
groups it was 0.13 ppm. Computer codes that implement these 14. N. H. Andersen, B. Cao, and C. Chen, Biochem. Biophys. Res.
ideas are available from the author, and equivalent code Commun., 1992, 184, 1008.
is part of the AMBER molecular modeling package, which 15. K. Ösapay and D. A. Case, J. Biomol. NMR, 1994, 4, 215.
also allows refinement of structures using penalty functions 16. I. D. Kuntz, P. A. Kosen, and E. C. Craig, J. Am. Chem. Soc.,
based on chemical shift formulas.56 Initial applications to 1991, 113, 1406.
myoglobin57 suggest that this idea may be a feasible and useful 17. M. A. Jiménez, F. J. Blanco, M. Rico, J. Santoro, J. Herranz, and
approach. J. L. Nieto, Eur. J. Biochem., 1992, 207, 39.

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This article was previously published in the Encyclopedia of Magnetic Resonance in 2007 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470034590.emrstm0008
 AMINO ACIDS, PEPTIDES & PROTEINS: CHEMICAL SHIFTS 5

18. N. E. Zhou, B. -Y. Zhu, B. D. Sykes, and R. S. Hodges, J. Am. 45. T. Asakura, Y. Niizawa, and M. P. Williamson, J. Magn. Reson.,
Chem. Soc., 1992, 114, 4320. 1992, 98, 646.
19. F. J. Blanco, J. Herranz, C. González, M. A. Jiménez, M. Rico, J. 46. R. F. Zürcher, Prog. Nucl. Magn. Reson. Spectrosc., 1967, 2,
Santoro, and J. L. Nieto, J. Am. Chem. Soc., 1992, 114, 9676. 205.
20. M. Bruix, M. Perello, J. Herranz, M. Rico, and J. L. Nieto, 47. M. P. Williamson and T. Asakura, J. Magn. Reson., 1991, 94,
Biochem. Biophys. Res. Commun., 1990, 167, 1009. 557.
21. S. Spera and A. Bax, J. Am. Chem. Soc., 1991, 113, 5490. 48. M. P. Williamson, T. Asakura, E. Nakamura, and M. Demura, J.
22. M. D. Reily, V. Thanabal, and D. O. Omecinsky, J. Am. Chem. Biomol. NMR, 1992, 2, 83.
Soc., 1992, 114, 6251. 49. J. Herranz, C. González, M. Rico, J. L. Nieto, J. Santoro, M. A.
23. D. W. Urry, L. W. Mitchell, and T. Ohnishi, Proc. Natl. Acad. Sci. Jiménez, M. Bruix, J. L. Neira, and F. J. Blanco, Magn. Reson.
USA, 1974, 71, 3265. Chem., 1992, 30, 1012.
24. T. Asakura, M. Kamio, and A. Nishioka, Biopolymers, 1979, 18, 50. M. P. Williamson and T. Asakura, J. Magn. Reson., Ser. B, 1993,
467. 101, 63.
25. S. Ando, I. Ando, A. Shoji, and T. Ozaki, J. Am. Chem. Soc., 1988, 51. J. Augspurger, J. G. Pearson, E. Oldfield, C. E. Dykstra, K. D.
110, 3380. Park, and D. Schwartz, J. Magn. Reson., 1992, 100, 342.
26. N. Asakawa, S. Kuroki, H. Kurosu, I. Ando, A. Shoji, and T. 52. J. D. Augspurger, A. C. de Dios, E. Oldfield, and C. E. Dykstra,
Ozaki, J. Am. Chem. Soc., 1992, 114, 3261. Chem. Phys. Lett., 1993, 213, 211.
27. E. Tüchsen and P. E. Hansen, Int. J. Biol. Macromol., 1991, 13, 53. J. G. Pearson, E. Oldfield, F. S. Lee, and A. Warshel, J. Am. Chem.
2. Soc., 1993, 115, 6851.
28. J. Glushka, M. Lee, S. Coffin, and D. Cowburn, J. Am. Chem. Soc., 54. C. Giessner-Prettre, M. T. Cung, and M. Marraud, Eur. J.
1989, 111, 7716. Biochem., 1987, 163, 79.
29. J. Glushka, M. Lee, S. Coffin, and D. Cowburn, J. Am. Chem. Soc., 55. N. Gresh and C. Giessner-Prettre, Biochem. Biophys. Res. Com-
1990, 112, 2843. mun., 1990, 171, 1211.
30. N. J. Skelton, M. Akke, J. Kördel, E. Thulin, S. Forsén, and W. J. 56. D. A. Pearlman, D. A. Case, J. C. Caldwell, G. L. Seibel, U. C.
Chazin, FEBS Lett., 1992, 303, 136. Singh, P. Weiner, and P. A. Kollman, AMBER 4.0 , University of
31. R. K. Harris, Nuclear Magnetic Resonance Spectroscopy, A California, San Francisco, CA, 1991.
Physicochemical View , Longman, Harlow, 1986. 57. D. A. Case and P. E. Wright, in NMR in Proteins, ed. G. M. Clore
32. W. H. Flygare, Chem. Rev., 1974, 74, 653. and A. Gronenborn, MacMillan, New York, 1993, pp. 53–91.
33. L. Pauling, Proc. Natl. Acad. Sci. USA, 1979, 76, 2293.
34. C. W. Haigh and R. B. Mallion, Prog. Nucl. Magn. Reson.
Spectrosc., 1980, 13, 303. Acknowledgments
35. H. M. McConnell, J. Chem. Phys., 1957, 27, 226.
This work was supported by NIH Grant GM45811. I thank Beverley
36. A. D. Buckingham, Can. J. Chem., 1960, 38, 300.
Seavey and John Markley for providing access to the BioMagResBank
37. C. Giessner-Prettre and B. Pullman, C. R. Hebd. Seances Acad., database, and Gene Merutka, Jane Dyson, Peter Wright, and Klara
Sci., Ser. D, 1969, 268, 1115. Ösapay for helpful discussions.
38. K. Ösapay and D. A. Case, J. Am. Chem. Soc., 1991, 113, 9436.
39. C. E. Johnson and F. A. Bovey, J. Chem. Phys., 1958, 29, 1012.
40. R. J. Abraham, Mol. Phys., 1961, 4, 145.
Biographical Sketches
41. R. J. Abraham, G. R. Bedford, D. McNeillie, and B. Wright, Org.
Magn. Reson., 1980, 14, 418.
David A. Case, b 1948. B.S., 1970, Michigan State, A.M., 1972,
42. R. J. Abraham, J. Magn. Reson., 1981, 43, 491. Harvard, Ph.D., 1977, Harvard, USA. Approx. 90 publications.
43. K. J. Cross and P. E. Wright, J. Magn. Reson., 1985, 64, 220. Research interests include modeling of proteins and nucleic acids,
44. H. L. Tigelaar and W. H. Flygare, J. Am. Chem. Soc., 1972, 94, quantum mechanical studies of the active sites of metalloenzymes, and
343. computational aspects of NMR.

eMagRes, Online © 2007 John Wiley & Sons, Ltd.

This article is © 2007 John Wiley & Sons, Ltd.
This article was previously published in the Encyclopedia of Magnetic Resonance in 2007 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470034590.emrstm0008