Calculation of chemical shift anisotropy in proteins

Abstract

Individual peptide groups in proteins must exhibit some variation in the chemical shift anisotropy (CSA) of their constituent atoms, but not much is known about the extent or origins of this dispersion. Direct spectroscopic measurement of CSA remains technically challenging, and theoretical methods can help to overcome these limitations by estimating shielding tensors for arbitrary structures. Here we use an automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach to compute 15N, 13C′ and 1H chemical shift tensors for human ubiquitin and the GB1 and GB3 fragments of staphylococcal protein G. The average and range of variation of the anisotropies is in good agreement with experimental estimates from solid-state NMR, and the variation among residues is somewhat smaller than that estimated from solution-state measurements. Hydrogen-bond effects account for much of the variation, both between helix and sheet regions, and within elements of secondary structure, but other effects (including variations in torsion angles) may play a role as well.

Coupling of Conformational Transitions in the N-terminal Domain of the 51-kDa FK506-binding Protein (FKBP51) Near Its Site of Interaction with the Steroid Receptor Proteins

“…In such a transition, the substantial exchange line broadening of the Lys-60 amide might reflect not only changes in the local backbone geometry of the ␤ 2 strand, it could also reflect alterations in the hydrogen bonding of the Gly-59 carbonyl oxygen, which serves as the acceptor for the bifurcated hydrogen bonds to the ␤ 3a strand. Disruption of hydrogen bonding at a peptide C ϭ O group is known to give rise to changes in the chemical shift for the peptide nitrogen resonance of several ppm (50).…”

Rotational velocity rescaling of molecular dynamics trajectories for direct prediction of protein NMR relaxation

“…GB3 and its close homolog GB1 have played a central role in the efforts to determine amide 15 N chemical shift tensors by solution phase relaxation, liquid crystal and cross-correlated relaxation, and solid state magicangle measurements as well as quantum mechanics predictions [24][25][26]. The magnetic field dependent 15 N relaxation measurements of Hall and Fushman [20] deduced a range of residue-specific CSA values from 111.3 to 240.8 ppm for GB3.…”

“…On the other hand, both 15 [38,42,43] are known to be sensitive to changes in hydrogen bond interactions. In particular, Tang and Case [26] have recently presented QM/MM calculations indicating the 15 N CSA value for specific peptide units in GB3 tend to increase in the order of no hydrogen bonding, hydrogen bonding to the N\H only, hydrogen bonding to C_O only, and hydrogen bonding at both the N\H and C_O. The increments of these changes in CSA values are on the order of 5 ppm.…”

“…Thus in contrast to larger proteins for which the T 1 values of the well-ordered amides increases proportionate to τ c , the T 1 values of such residues in GB3 are less sensitive to the effective τ c than are the T 2 values. This relaxation behavior has also contributed to GB3 and its close homolog GB1 having become the favorite system for analyzing residue-dependent variations in the amide 15 N chemical shift tensor by magnetic field dependent solution phase relaxation measurements [20], liquid crystal and cross-correlated relaxation measurements [21], and solid state magic-angle measurements [22,23] as well as quantum mechanics predictions [24][25][26]. The present analysis provides an effective basis for assessing the utility of the sitespecific 15 N chemical shift anisotropy (CSA) values obtained by these various experimental techniques in providing NMR relaxation predictions.…”

An extrapolation method for the efficient calculation of molecular response properties within Born–Oppenheimer molecular dynamics

“…This renders the restriction to just a few snapshots often mandatory, which typically leads to insufficient sampling for reliable predictions. The difficulties of sufficient and efficient sampling for the ab initio simulation of, e.g., NMR spectra characterized by chemical shieldings, spin-spin coupling constants, chemical shift anisotropies (CSA), and nuclear spin relaxation [1][2][3][4][5] are abundant, so that increased efficiency by transferring information between sampling points in order to speed up calculations is important and the focus of the present paper.…”