Multiscale Modeling of the Active Site of [Fe] Hydrogenase: The H-2 Binding Site in Open and Closed Protein Conformations

Research output: Contribution to journalArticle


A series of QM/MM optimizations of the full protein of [Fe] hydrogenase were performed. The FeGP cofactor has been optimized in the water-bound resting state (1), with a side-on bound dihydrogen (2), or as a hydride intermediate (3). For inclusion of H4MPT in the closed structure, advanced multiscale modeling appears to be necessary, especially to obtain reliable distances between CH-H4MPT+ and the dihydrogen (H-2) or hydride (H-) ligand in the FeGP cofactor. Inclusion of the full protein is further important for the relative energies of the two intermediates 2 and 3. We finally find that hydride transfer from 3 has a significantly higher barrier than found in previous studies neglecting the full protein environment.


  • Erik Donovan Hedegard
  • Jacob Kongsted
  • Ulf Ryde
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biophysics
  • Theoretical Chemistry


  • [Fe] hydrogenase, hydrogen activation, molecular mechanics, multiscale, modeling, quantum mechanics
Original languageEnglish
Pages (from-to)6246-6250
JournalAngewandte Chemie (International edition)
Issue number21
Publication statusPublished - 2015
Publication categoryResearch

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)