How the water-soluble hemicarcerand incarcerates guests at room temperature decoded with modular simulations

Katherine G. McFerrin, Yuan Ping Pang

Research output: Contribution to journalArticlepeer-review


Molecular dynamics simulations of hemicarcerands and related variants allow the study of constrictive binding and offer insight into the rules of molecular complexation, but are limited because three-dimensional models of hemicarcerands are tedious to build and their atomic charges are complicated to derive. There have been no molecular dynamics simulations of the reported water-soluble hemicarcerand (Octacid4) that explain how Octacid4 encapsulates guests at 298 K and keeps them encapsulated at 298 K in NMR experiments. Herein we report a modular approach to hemicarcerand simulations that simplifies the model building and charge derivation in a manner reminiscent of the approach to protein simulations with truncated amino acids as building blocks. We also report that in aqueous molecular dynamics simulations at 298 K apo Octacid4 adopts two clusters of conformations one of which has an equatorial portal open but the guest-bound Octacid4 adopts one cluster of conformations with all portals closed. These results explain how Octacid4 incarcerates guests at room temperature and suggest that the guest-induced host conformational change that impedes decomplexation is a previously unrecognized conformational characteristic that promotes strong molecular complexation.

Original languageEnglish (US)
Article number26
JournalCommunications Chemistry
Issue number1
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Biochemistry
  • General Chemistry
  • Environmental Chemistry
  • Materials Chemistry


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