Density functional calculations of 15N chemical shifts in solvated dipeptides

Cai, Ling; Fushman, David; Kosov, Daniel S.

doi:10.1007/s10858-008-9241-7

Cited by 24 publications

(107 citation statements)

References 53 publications

(60 reference statements)

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“…(2-8) Factors contributing to 15 N chemical shifts are less understood than those for 1 H and 13 C nuclei and can vary from the type of the amino acid to torsion angles, hydrogen bonding patterns and others. (9-13) In many solution NMR backbone dynamics studies, a single value of CSA is used for all residues and several works have looked into the validity of this approximation. For example, Loth et al(14) and Yao et al(3) found a considerable extent of residue-specific variations.…”

Section: Introductionmentioning

confidence: 99%

15N CSA tensors and 15N–1H dipolar couplings of protein hydrophobic core residues investigated by static solid-state NMR

Vugmeyster

Ostrovsky

2015

Journal of Magnetic Resonance

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In this work, we assess the usefulness of static 15N NMR techniques for the determination of the 15N chemical shift anisotropy (CSA) tensor parameters and 15N-1H dipolar splittings in powder protein samples. By using five single labeled samples of the villin headpiece subdomain protein in a hydrated lyophilized powder state, we determine the backbone 15N CSA tensors at two temperatures, 22 and –35°C, in order to get a snapshot of the variability across the residues and as a function of temperature. All sites probed belonged to the hydrophobic core and most of them were part of α-helical regions. The values of the anisotropy (which include the effect of the dynamics) varied between 130 and 156 ppm at 22°C, while the values of the asymmetry were in the 0.32–0.082 range. The Leu-75 and Leu-61 backbone sites exhibited high mobility based on the values of their temperature-dependent anisotropy parameters. Under the assumption that most differences stem from dynamics, we obtained the values of the motional order parameters for the 15N backbone sites. While a simple one-dimensional line shape experiment was used for the determination of the 15N CSA parameters, a more advanced approach based on the “magic sandwich” SAMMY pulse sequence (Nevzorov & Opella, J. Magn. Reson. (2003) 164, 182-186) was employed for the determination of the 15N-1H dipolar patterns, which yielded estimates of the dipolar couplings. Accordingly, the motional order parameters for the dipolar interaction were obtained. It was found that the order parameters from the CSA and dipolar measurements are highly correlated, validating that the variability between the residues is governed by the differences in dynamics. The values of the parameters obtained in this work can serve as reference values for developing more advanced magic-angle spinning recoupling techniques for multiple labeled samples.

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Section: Introductionmentioning

confidence: 99%

15N CSA tensors and 15N–1H dipolar couplings of protein hydrophobic core residues investigated by static solid-state NMR

Vugmeyster

Ostrovsky

2015

Journal of Magnetic Resonance

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“…Fourth, there are systematic errors associated with the level of theory used and the basis set chosen for calculating the electronic structure. In practice, an offset may exist that will need to be corrected if an absolute isotropic chemical shift prediction is the aim (Cai et al 2008). An additional complication here is that this correction should differ between various residue types (Xu and Case 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Previous theoretical works (de Dios et al 1993b; Le and Oldfield 1996; Xu and Case 2002; Cai et al 2008) have established that 15 N chemical shielding depends on the following factors with none seemingly dominating: ϕ, ψ, χ 1 , preceding side chain’s identity and conformation, hydrogen bonding partners, electrostatic interactions, and solvent effect. Whereas the short-range interaction with hydrogen-bonding partners can be included explicitly and exactly, model treatment has been required for long-range electrostatic interactions.…”

Section: Introductionmentioning

confidence: 99%

Density functional calculations of chemical shielding of backbone 15N in helical residues of protein G

2009

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Summary We performed density functional calculations of backbone 15N chemical shielding tensors in selected helical residues of protein G. Here we describe a computationally efficient methodology to include most of the important effects in the calculation of chemical shieldings of backbone 15N. We analyzed the role of long-range intra-protein electrostatic interactions by comparing models with different complexity in vacuum and in charge field. Our results show that the dipole moment of the α-helix can cause significant deshielding of 15N; therefore, it needs to be considered when calculating 15N chemical shielding. We found that it is important to include interactions with the side chains that are close in space when the charged form for ionizable side chains is adopted in the calculation. We also illustrate how the ionization state of these side chains can affect the chemical shielding tensor elements. Chemical shielding calculations using a 8-residue fragment model in vacuum and adopting the charged form of ionizable side chains yield a generally good agreement with experimental data.

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“…We have previously shown that use of a force field in which experimental 13 Cα CSTs are compared with ab initio CSTs [generated as a function of backbone conformation (ϕ, ψ)] significantly improves the precision and accuracy of SSNMR-computed protein structures (10). In addition to determination of NMR-based structures and dynamics, CST datasets are invaluable for the continued development of quantum chemical techniques to compute isotropic and anisotropic chemical shifts, furthering our understanding of appropriate basis sets and functions for accurate MO theory of proteins (4,6,11,(25)(26)(27).Over the past decade, protein structure determination by SSNMR has progressed substantially in terms of the rate of data collection and analysis, as well as in the resolution and complexity of the resulting structures (10,(28)(29)(30)(31)(32)(33)(34)(35)(36). In most cases, structures have been determined by using a combination of semiquantitative distance restraints (comparable to solution NOEs) together with semiempirical dihedral angle restraints, obtained from isotropic chemical shifts and chemical shift databases.…”

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Ultrahigh resolution protein structures using NMR chemical shift tensors

Wylie

Sperling

Nieuwkoop

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

158

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NMR chemical shift tensors (CSTs) in proteins, as well as their orientations, represent an important new restraint class for protein structure refinement and determination. Here, we present the first determination of both CST magnitudes and orientations for 13 Cα and 15 N (peptide backbone) groups in a protein, the β1 IgG binding domain of protein G from Streptococcus spp., GB1. Site-specific 13 Cα and 15 N CSTs were measured using synchronously evolved recoupling experiments in which 13 C and 15 N tensors were projected onto the 1 H-13 C and 1 H-15 N vectors, respectively, and onto the 15 N-13 C vector in the case of 13 Cα. The orientations of the 13 Cα CSTs to the 1 H-13 C and 13 C-15 N vectors agreed well with the results of ab initio calculations, with an rmsd of approximately 8°. In addition, the measured 15 N tensors exhibited larger reduced anisotropies in α-helical versus β-sheet regions, with very limited variation (18 AE 4°) in the orientation of the z-axis of the 15 N CST with respect to the 1 H-15 N vector. Incorporation of the 13 Cα CST restraints into structure calculations, in combination with isotropic chemical shifts, transferred echo double resonance 13 C-15 N distances and vector angle restraints, improved the backbone rmsd to 0.16 Å (PDB ID code 2LGI) and is consistent with existing X-ray structures (0.51 Å agreement with PDB ID code 2QMT). These results demonstrate that chemical shift tensors have considerable utility in protein structure refinement, with the best structures comparable to 1.0-Å crystal structures, based upon empirical metrics such as Ramachandran geometries and χ 1 ∕χ 2 distributions, providing solid-state NMR with a powerful tool for de novo structure determination.magic-angle spinning | dihedral angles | cross validation | nanocrystal | quantum chemistry T he chemical shift is an exquisite and powerful probe of molecular structure, deriving from the interaction of molecular orbitals with an external magnetic field, B 0 . Understanding the relationships between chemical shifts and protein structure has substantial implications for modern nuclear magnetic resonance (NMR) spectroscopy, chemistry, and structural biology (1-12). The chemical shift tensor (CST) is rich with information, even when two-thirds of it is averaged to zero by molecular tumbling in solution or magic-angle spinning (MAS) of solid samples. The remaining isotopic chemical shifts remain an excellent resource for structure determination and validation, and higher-order interactions of the CST have substantial contributions to NMR relaxation (13-19). Therefore, detailed knowledge of CSTs permits a precise analysis of motion (20)(21)(22). Solid-state NMR (SSNMR) of fully aligned samples exploits amide 15 N tensor information to determine the orientations of helices relative to the bilayer (23, 24). We have previously shown that use of a force field in which experimental 13 Cα CSTs are compared with ab initio CSTs [generated as a function of backbone conformation (ϕ, ψ)] significantly improves the precision and...

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Density functional calculations of 15N chemical shifts in solvated dipeptides

Cited by 24 publications

References 53 publications

15N CSA tensors and 15N–1H dipolar couplings of protein hydrophobic core residues investigated by static solid-state NMR

15N CSA tensors and 15N–1H dipolar couplings of protein hydrophobic core residues investigated by static solid-state NMR

Density functional calculations of chemical shielding of backbone 15N in helical residues of protein G

Ultrahigh resolution protein structures using NMR chemical shift tensors

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