Quantum chemical evaluation of protein control over heme ligation: CO/O 2 Discrimination in myoglobin

Filippo De Angelis, Andrzej A. Jarzȩcki, Roberto Car, Thomas G. Spiro

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Control of O 2 versus CO binding in myoglobin (Mb) is tuned by a distal histidine residue through steric and H-bonding interactions. These interactions have been evaluated via Car-Parrinello DFT calculations, whose efficiency allows full quantum mechanical treatment of the 13 closest residues surrounding the heme. The small (8°) deviation of the Fe-C-O bond angle from linearity results from the steric influence of a distal valine residue and not the distal histidine. H-bond energies were evaluated by replacing the distal histidine with the non-H-bonding residue isoleucine. Binding energies for CO and O 2 decreased by 0.8 and 4.1 kcal/ mol for MbCO and MbO 2, in good agreement with experimental H-bond estimates. Ligand discrimination is dominated by distal histidine H-bonding, which is also found to stabilize a metastable side-on isomer of MbO 2 that may play a key role in MbO 2 photodynamics.

Original languageEnglish (US)
Pages (from-to)3065-3070
Number of pages6
JournalJournal of Physical Chemistry B
Issue number7
StatePublished - Feb 24 2005

All Science Journal Classification (ASJC) codes

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


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