NMR Parameters in Proteins and Nucleic Acids

Case, David A.

doi:10.1002/3527601678.ch21

Cited by 4 publications

(5 citation statements)

References 44 publications

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“…In the study of the relationship between the NMR chemical shifts and the structure, quantum chemical calculations of magnetic shielding have long been used . Nuclear magnetic shielding is a response property that can be defined quantum mechanically and directly calculated.…”

Section: Introductionmentioning

confidence: 99%

Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and ¹³C NMR Chemical Shift Tensors

Bouzková

Babinský

Novosadová

et al. 2013

J. Chem. Theory Comput.

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An understanding of the role of intermolecular interactions in crystal formation is essential to control the generation of diverse crystalline forms which is an important concern for pharmaceutical industry. Very recently, we reported a new approach to interpret the relationships between intermolecular hydrogen bonding, redistribution of electron density in the system, and NMR chemical shifts (Babinský et al. J. Phys. Chem. A, 2013, 117, 497). Here, we employ this approach to characterize a full set of crystal interactions in a sample of anhydrous theobromine as reflected in (13)C NMR chemical shift tensors (CSTs). The important intermolecular contacts are identified by comparing the DFT-calculated NMR CSTs for an isolated theobromine molecule and for clusters composed of several molecules as selected from the available X-ray diffraction data. Furthermore, electron deformation density (EDD) and shielding deformation density (SDD) in the proximity of the nuclei involved in the proposed interactions are calculated and visualized. In addition to the recently reported observations for hydrogen bonding, we focus here particularly on the stacking interactions. Although the principal relations between the EDD and CST for hydrogen bonding (HB) and stacking interactions are similar, the real-space consequences are rather different. Whereas the C-H···X hydrogen bonding influences predominantly and significantly the in-plane principal component of the (13)C CST perpendicular to the HB path and the C═O···H hydrogen bonding modulates both in-plane components of the carbonyl (13)C CST, the stacking modulates the out-of-plane electron density resulting in weak deshielding (2-8 ppm) of both in-plane principal components of the CST and weak shielding (∼ 5 ppm) of the out-of-plane component. The hydrogen-bonding and stacking interactions may add to or subtract from one another to produce total values observed experimentally. On the example of theobromine, we demonstrate the power of this approach to identify and classify the intermolecular forces that govern the packing motifs in crystals and modulate the NMR CSTs.

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Section: Introductionmentioning

confidence: 99%

Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and ¹³C NMR Chemical Shift Tensors

Bouzková

Babinský

Novosadová

et al. 2013

J. Chem. Theory Comput.

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“…An accurate theoretical prediction of absolute values of chemical shifts is an extremely difficult task – . Indeed, calculated chemical shifts differ from experiment by approximately −8 ppm ( 15 N), +7 ppm ( 13 C α ), and +2.5 ppm ( 13 C β ) even with structures 8 and 9 .…”

Section: Resultsmentioning

confidence: 99%

“…Ab initio studies on peptide and protein chemical shifts have been recently reviewed by David Case whose group, together with the group of Michael Barfield, did the pioneering work in the field of calculations on static models – . Sitkoff and Case probed van der Waals dispersion, electrostatic, magnetic anisotropy, as well as H–bond effects on a dipeptide and found a good agreement between density functional theory (DFT) results and empirical formulas . Xu and Case carried out DFT calculations on larger peptides up to 21 amino acids and used the results, in conjunction with an additive model of chemical shift contributions, to create an algorithm for a prediction of 15 N and 13 C shifts in proteins .…”

Section: Introductionmentioning

confidence: 99%

The influence of Mg²⁺ coordination on ¹³C and ¹⁵N chemical shifts in CKI1_RD protein domain from experiment and molecular dynamics/density functional theory calculations

et al. 2016

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Sequence dependence of (13) C and (15) N chemical shifts in the receiver domain of CKI1 protein from Arabidopsis thaliana, CKI1RD , and its complexed form, CKI1RD •Mg(2+), was studied by means of MD/DFT calculations. MD simulations of a 20-ns production run length were performed. Nine explicitly hydrated structures of increasing complexity were explored, up to a 40-amino-acid structure. The size of the model necessary depended on the type of nucleus, the type of amino acid and its sequence neighbors, other spatially close amino acids, and the orientation of amino acid NH groups and their surface/interior position. Using models covering a 10 and a 15 Å environment of Mg(2+), a semi-quantitative agreement has been obtained between experiment and theory for the V67-I73 sequence. The influence of Mg(2+) binding was described better by the 15 Å as compared to the 10 Å model. Thirteen chemical shifts were analyzed in terms of the effect of Mg(2+) insertion and geometry preparation. The effect of geometry was significant and opposite in sign to the effect of Mg(2+) binding. The strongest individual effects were found for (15) N of D70, S74, and V68, where the electrostatics dominated; for (13) Cβ of D69 and (15) N of K76, where the influences were equal, and for (13) Cα of F72 and (13) Cβ of K76, where the geometry adjustment dominated. A partial correlation between dominant geometry influence and torsion angle shifts upon the coordination has been observed.

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“…11 ppm with respect to experimental values of refs and , when we compare the steps predominantly found in the BI state. This offset originates partly from the application of a limited model and partly from systematically underestimated P–O bond lengths used in the molecular dynamics as compared to the DFT-optimized geometries . The latter problem can be partially overcome by using geometries from CPMD snapshots, as discussed below.…”

Section: Resultsmentioning

confidence: 99%

Toward Reproducing Sequence Trends in Phosphorus Chemical Shifts for Nucleic Acids by MD/DFT Calculations

Přecechtělová¹,

Munzarová²,

Vaara

et al. 2013

J. Chem. Theory Comput.

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This work addresses the question of the ability of the molecular dynamics-density functional theory (MD/DFT) approach to reproduce sequence trend in (31)P chemical shifts (δP) in the backbone of nucleic acids. δP for [d(CGCGAATTCGCG)]2, a canonical B-DNA, have been computed using density functional theory calculations on model compounds with geometries cut out of snapshots of classical molecular dynamics (MD) simulations. The values of (31)P chemical shifts for two distinct B-DNA subfamilies BI and BII, δP/BI and δP/BII, have been determined as averages over the BI and BII subparts of the MD trajectory. This has been done for various samplings of MD trajectory and for two sizes of both the model and the solvent embedding. For all of the combinations of trajectory sampling, model size, and embedding size, sequence dependence of δP/BI in the order of 0.4-0.5 ppm has been obtained. Weighted averages for individual (31)P nuclei in the studied DNA double-helix have been calculated from δP/BI and δP/BII using BI and BII percentages from free MD simulations as well as from approaches employing NMR structural restraints. A good qualitative agreement is found between experimental sequence trends in δP and theoretical δP employing short (24 ns) MD run and BI, BII percentages determined by Hartmann et al. or via MD with the inclusion of NMR structural restraints. Theoretical δP exhibit a systematic offset of ca. 11 ppm and overestimation of trends by a factor of ca. 1.7. When scaled accordingly, theoretical δP/BI and δP/BII can be used to determine the expected percentage of BII to match the experimental value of δP. As evidenced by the calculations on snapshots from Car-Parrinello molecular dynamics, the systematic offsets of the theoretical δP obtained by MD/DFT approach result primarily from the unrealistic bond lengths employed by classical MD. The findings made in this work provide structure-δP relationships for possible use as NMR restraints and suggest that NMR calculations on MD snapshots can be in the future employed for the validation of newly developed force fields.

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NMR Parameters in Proteins and Nucleic Acids

Cited by 4 publications

References 44 publications

Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and ¹³C NMR Chemical Shift Tensors

Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and ¹³C NMR Chemical Shift Tensors

The influence of Mg²⁺ coordination on ¹³C and ¹⁵N chemical shifts in CKI1_RD protein domain from experiment and molecular dynamics/density functional theory calculations

Toward Reproducing Sequence Trends in Phosphorus Chemical Shifts for Nucleic Acids by MD/DFT Calculations

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NMR Parameters in Proteins and Nucleic Acids

Cited by 4 publications

References 44 publications

Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and 13C NMR Chemical Shift Tensors

Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and 13C NMR Chemical Shift Tensors

The influence of Mg2+ coordination on 13C and 15N chemical shifts in CKI1RD protein domain from experiment and molecular dynamics/density functional theory calculations

Toward Reproducing Sequence Trends in Phosphorus Chemical Shifts for Nucleic Acids by MD/DFT Calculations

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Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and ¹³C NMR Chemical Shift Tensors

Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and ¹³C NMR Chemical Shift Tensors

The influence of Mg²⁺ coordination on ¹³C and ¹⁵N chemical shifts in CKI1_RD protein domain from experiment and molecular dynamics/density functional theory calculations