title: The application of tailor-made force fields and molecular dynamics for NMR crystallography: a case study of free base cocaine.
abstract: Motional averaging has been proven to be significant in predicting the chemical shifts inab initiosolid-state NMR calculations, and the applicability of motional averaging with molecular dynamics has been shown to depend on the accuracy of the molecular mechanical force field. The performance of a fully automatically generated tailor-made force field (TMFF) for the dynamic aspects of NMR crystallography is evaluated and compared with existing benchmarks, including static dispersion-corrected density functional theory calculations and the COMPASS force field. The crystal structure of free base cocaine is used as an example. The results reveal that, even though the TMFF outperforms the COMPASS force field for representing the energies and conformations of predicted structures, it does not give significant improvement in the accuracy of NMR calculations. Further studies should direct more attention to anisotropic chemical shifts and development of the method of solid-state NMR calculations.
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark.
authors.forename: Xiaozhou
authors.identifier: https://orcid.org/0000-0003-3882-7073
authors.initials: X
authors.lastname: Li
authors.affiliation: Avant-garde Materials Simulation Deutschland GmbH, Rosa-Luxemberg-Strasse 14, Freiburg D-79100, Germany.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Neumann
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark.
authors.forename: Jacco
authors.identifier: https://orcid.org/0000-0002-3026-4213
authors.initials: J
authors.lastname: van de Streek
keywords: NMR crystallography; cocaine free base; crystal structure prediction; density functional theory; molecular dynamics