Conformational Sampling by Ab Initio Molecular Dynamics Simulations Improves NMR Chemical Shift Predictions

Dračínský, Martin; Möller, Heiko M.; Exner, Thomas E.

doi:10.1021/ct400282h

Cited by 50 publications

(42 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dračínský et al also encourage using predicted NMR chemical shifts as a way of evaluating new MD force fields. In their study comparing ab initio MD and classical MD for dynamic averaging, they found that ab initio MD allowed for better conformational sampling, especially for N‐H distances.…”

Section: Conformational Averagingmentioning

confidence: 99%

Calculating nuclear magnetic resonance chemical shifts in solvated systems

Casabianca

2020

Magnetic Reson in Chemistry

View full text Add to dashboard Cite

The nuclear magnetic resonance (NMR) chemical shift is extremely sensitive to molecular geometry, hydrogen bonding, solvent, temperature, pH, and concentration. Calculated magnetic shielding constants, converted to chemical shifts, can be valuable aids in NMR peak assignment and can also give detailed information about molecular geometry and intermolecular effects. Calculating chemical shifts in solution is complicated by the need to include solvent effects and conformational averaging. Here, we review the current state of NMR chemical shift calculations in solution, beginning with an introduction to the theory of calculating magnetic shielding in general, then covering methods for inclusion of solvent effects and conformational averaging, and finally discussing examples of applications using calculated chemical shifts to gain detailed structural information.

show abstract

Section: Conformational Averagingmentioning

confidence: 99%

Calculating nuclear magnetic resonance chemical shifts in solvated systems

Casabianca

2020

Magnetic Reson in Chemistry

View full text Add to dashboard Cite

show abstract

“…Solely conducting MD simulations and taking a few snapshots for the DFT‐based NMR parameter calculation as proposed by Kwan and Liu23 (see also Ref. 24) does not solve the problem either because a proper average cannot be obtained in this way with reasonable effort, and furthermore, somewhat higher but still thermally accessible barriers (5–10 kcal mol − 1 ) are very difficult to overcome. A very important “side product” of our procedure is that in case of a reasonable coincidence of experimental and theoretical spectra, knowledge of the dominantly contributing conformers under the measurement conditions is obtained.…”

mentioning

confidence: 99%

Fully Automated Quantum‐Chemistry‐Based Computation of Spin–Spin‐Coupled Nuclear Magnetic Resonance Spectra

et al. 2017

View full text Add to dashboard Cite

We present a composite procedure for the quantum‐chemical computation of spin–spin‐coupled 1H NMR spectra for general, flexible molecules in solution that is based on four main steps, namely conformer/rotamer ensemble (CRE) generation by the fast tight‐binding method GFN‐xTB and a newly developed search algorithm, computation of the relative free energies and NMR parameters, and solving the spin Hamiltonian. In this way the NMR‐specific nuclear permutation problem is solved, and the correct spin symmetries are obtained. Energies, shielding constants, and spin–spin couplings are computed at state‐of‐the‐art DFT levels with continuum solvation. A few (in)organic and transition‐metal complexes are presented, and very good, unprecedented agreement between the theoretical and experimental spectra was achieved. The approach is routinely applicable to systems with up to 100–150 atoms and may open new avenues for the detailed (conformational) structure elucidation of, for example, natural products or drug molecules.

show abstract

“…The calculated isotropic shielding constants were averaged over all sampled configurations and subtracted from the corresponding shielding constant of tetramethylsilane (TMS) computed at the same QM level of theory. 125,126 In this way, the combined effects of solvent and its influence on the local geometry of the G-quadruplex, on calculated chemical shifts, are taken into account. For comparison, we have also carried out analogous calculations based on configurations obtained by classical optimization at the AMBER MM level and for the X-ray structure.…”

Section: Resultsmentioning

confidence: 99%

MoD-QM/MM Structural Refinement Method: Characterization of Hydrogen Bonding in the Oxytricha nova G-Quadruplex

Newcomer

Ragain

et al. 2014

J. Chem. Theory Comput.

View full text Add to dashboard Cite

A generalization of the Moving-Domain Quantum Mechanics/Molecular Mechanics (MoD-QM/MM) hybrid method [Gascon, J. A.; Leung, S. S. F.; Batista, E. R.; Batista, V. S. J. Chem. Theory Comput. 2006, 2, 175– 186] is introduced to provide a self-consistent computational protocol for structural refinement of extended systems. The method partitions the system into molecular domains that are iteratively optimized as quantum mechanical (QM) layers embedded in their surrounding molecular environment to obtain an ab initio quality description of the geometry and the molecular electrostatic potential of the extended system composed of those constituent fragments. The resulting methodology is benchmarked as applied to model systems that allow for full QM optimization as well as through refinement of the hydrogen bonding geometry in Oxytricha nova guanine quadruplex for which several studies have been reported, including the X-ray structure and NMR data. Calculations of 1H NMR chemical shifts based on the gauge independent atomic orbital (GIAO) method and direct comparisons with experiments show that solvated MoD-QM/MM structures, sampled from explicit solvent molecular dynamics simulations, allow for NMR simulations in much improved agreement with experimental data than models based on the X-ray structure or those optimized using classical molecular mechanics force fields.

show abstract

Conformational Sampling by Ab Initio Molecular Dynamics Simulations Improves NMR Chemical Shift Predictions

Cited by 50 publications

References 80 publications

Calculating nuclear magnetic resonance chemical shifts in solvated systems

Calculating nuclear magnetic resonance chemical shifts in solvated systems

Fully Automated Quantum‐Chemistry‐Based Computation of Spin–Spin‐Coupled Nuclear Magnetic Resonance Spectra

MoD-QM/MM Structural Refinement Method: Characterization of Hydrogen Bonding in the Oxytricha nova G-Quadruplex

Contact Info

Product

Resources

About