An atomistic model for simulations of the general anesthetic isoflurane

Jërôme Hénni, Grace Brannigan, William P. Dailey, Roderic Eckenhoff, Michael L. Klein

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


An atomistic model of isoflurane is constructed and calibrated to describe its conformational preferences and intermolecular interactions. The model, which is compatible with the CHARMM force field for biomolecules, is based on target quantities including bulk liquid properties, molecular conformations, and local interactions with isolated water molecules. Reference data is obtained from tabulated thermodynamic properties and highresolution structural information from gas-phase electron diffraction, as well as DFT calculations at the B3LYP level. The model is tested against experimentally known solvation properties in water and oil, and shows quantitative agreement. In particular, isoflurane is faithfully described as lipophilic, yet nonhydrophobic, a combination of properties critical to its pharmocological activity. Intermolecular interactions of the model are further probed through simulations of the binding of isoflurane to a binding site in horse spleen apoferritin (HSAF). The observed binding mode compares well with crystallographic data, and the calculated binding affinities are compatible with experimental results, although both computational and experimental measurements are challenging and provide results with limited precision. The model is expected to be useful for detailed simulations of the elementary molecular processes associated with anesthesia. Full parameters are provided as Supporting Information.

Original languageEnglish (US)
Pages (from-to)604-612
Number of pages9
JournalJournal of Physical Chemistry B
Issue number1
StatePublished - Jan 14 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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