Well-Tempered Metadynamics Simulations Predict the Structural and Dynamic Properties of a Chiral 24-Atom Macrocycle in Solution.

ABSTRACT: Inspired by therapeutic potential, the molecular engineering of macrocycles is garnering increased interest. Exercising control with design, however, is challenging due to the dynamic behavior that these molecules must demonstrate in order to be bioactive. Herein, the value of metadynamics simulations is demonstrated: the free-energy surfaces calculated reveal folded and flattened accessible conformations of a 24-atom macrocycle separated by barriers of ∼6 kT under experimentally relevant conditions. Simulations reveal that the dominant conformer is folded-an observation consistent with a solid-state structure determined by X-ray crystallography and a network of rOes established by ¹H NMR. Simulations suggest that the macrocycle exists as a rapidly interconverting pair of enanti

SUBMITTER: Capelli R 

PROVIDER: S-EPMC9434777 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature