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Structure determination of an amorphous drug through large-scale NMR predictions
- Source :
- Nature Communications, Vol 12, Iss 1, Pp 1-8 (2021), Nature Communications
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
Abstract
- Knowledge of the structure of amorphous solids can direct, for example, the optimization of pharmaceutical formulations, but atomic-level structure determination in amorphous molecular solids has so far not been possible. Solid-state nuclear magnetic resonance (NMR) is among the most popular methods to characterize amorphous materials, and molecular dynamics (MD) simulations can help describe the structure of disordered materials. However, directly relating MD to NMR experiments in molecular solids has been out of reach until now because of the large size of these simulations. Here, using a machine learning model of chemical shifts, we determine the atomic-level structure of the hydrated amorphous drug AZD5718 by combining dynamic nuclear polarization-enhanced solid-state NMR experiments with predicted chemical shifts for MD simulations of large systems. From these amorphous structures we then identify H-bonding motifs and relate them to local intermolecular complex formation energies.<br />Determining the structure of amorphous solids is important for optimization of pharmaceutical formulations, but direct relation of molecular dynamics (MD) simulations and NMR to achieve this is challenging. Here, the authors use a machine learning model of chemical shifts to solve the atomic-level structure of the hydrated amorphous drug AZD5718 by combining dynamic nuclear polarization-enhanced solid-state NMR with predicted shifts for MD simulations of large systems.
- Subjects :
- spectroscopy
Materials science
Magnetic Resonance Spectroscopy
Scale (ratio)
Chemistry, Pharmaceutical
Science
h-1
Structure (category theory)
General Physics and Astronomy
Molecular Dynamics Simulation
Molecular dynamics
010402 general chemistry
molecular-dynamics simulation
01 natural sciences
Solid-state NMR
General Biochemistry, Genetics and Molecular Biology
Article
benchmark
Molecular solid
Structure prediction
0103 physical sciences
crystal-structure prediction
chemical-shift predictions
Multidisciplinary
Crystallography
010304 chemical physics
Molecular Structure
Chemical shift
Intermolecular force
Hydrogen Bonding
c-13
General Chemistry
0104 chemical sciences
Amorphous solid
Solid-state nuclear magnetic resonance
Chemical physics
Pyrazoles
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....2dddfa2f02f880b983eba8d0a6eaec35