RT Journal Article
T1 Unraveling the Catalytic Mechanism of β‑Cyclodextrin in the Vitamin D Formation
A1 Ferro Costas, David
A1 Sánchez-Murcia, Pedro A.
A1 Fernández Ramos, Antonio
K1 Cyclodextrin
K1 Encapsulation
K1 Catalysis
K1 Vitamin D
K1 Rate constant
AB Previous experimental studies have shown that the isomerization reaction of previtamin D3 (PreD3) to vitamin D3 (VitD3) is accelerated 40-fold when it takes place within a β-cyclodextrin dimer, in comparison to the reaction occurring in conventional isotropic solutions. In this study, we employ quantum mechanics-based molecular dynamics (MD) simulations and statistical multistructural variational transition state theory to unveil the origin of this acceleration. We find that the conformational landscape in the PreD3 isomerization is highly dependent on whether the system is encapsulated. In isotropic media, the triene moiety of the PreD3 exhibits a rich torsional flexibility. However, when encapsulated, such a flexibility is limited to a more confined conformational space. In both scenarios, our calculated rate constants are in close agreement with experimental results and allow us to identify the PreD3 flexibility restriction as the primary catalytic factor. These findings enhance our understanding of VitD3 isomerization and underscore the significance of MD and environmental factors in biochemical modeling.
PB American Chemical Society
SN 1549-9596
YR 2024
FD 2024
LK https://hdl.handle.net/10347/44414
UL https://hdl.handle.net/10347/44414
LA eng
NO J. Chem. Inf. Model. 2024, 64, 3865−3873
NO This work was partially supported by the Consellería de Cultura, Educación e Ordenación Universitaria (Centro singular de investigación de Galicia acreditación 2019–2022, ED431G 2019/03 and Grupo de referencia competitiva ED431C 2021/40), the European Regional Development Fund (ERDF), and the Ministerio de Ciencia e Innovación through Grant PID2019-107307RB-I00.
DS Minerva
RD 3 may 2026