First Principles Calculation of the Reaction Rates for Ligand Binding to Myoglobin: The Cases of NO and CO

Anikó Lábas, Dóra K. Menyhárd, Jeremy N. Harvey, J. Oláh

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Ligand binding by proteins is among the most fundamental processes in nature. Among these processes the binding of small gas molecules, such as O2, CO and NO to heme proteins has traditionally received vivid interest, which was further boosted by their recently recognized significant role in gas sensing in the body. At the heart of the binding of these ligands to the heme group is the spinforbidden reaction between high-spin iron(II) and the ligand yielding a low-spin adduct. We use computational means to address the complete mechanism of CO and NO binding by myoglobin. Considering that it involves several steps occurring on different time scales, molecular dynamics simulations were performed to address the diffusion of the ligand through the enzyme, and DFT calculations in combination with statistical rate calculation to investigate the spin-forbidden reaction. The calculations yielded rate constants in qualitative agreement with experiments and revealed that the bottleneck of NO and CO binding is different; for NO, diffusion was found to be rate-limiting, whereas for CO, the spin-forbidden step is the slowest.

Original languageEnglish
Pages (from-to)5350-5358
Number of pages9
JournalChemistry - A European Journal
Volume24
Issue number20
DOIs
Publication statusPublished - Apr 6 2018

Fingerprint

Myoglobin
Carbon Monoxide
Reaction rates
Ligands
Gases
Hemeproteins
Heme
Discrete Fourier transforms
Molecular dynamics
Rate constants
Carrier Proteins
Iron
Enzymes
Proteins
Molecules
Computer simulation
Experiments

Keywords

  • heme
  • ligand binding
  • molecular dynamics
  • quantum chemistry
  • spin-forbidden

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

First Principles Calculation of the Reaction Rates for Ligand Binding to Myoglobin : The Cases of NO and CO. / Lábas, Anikó; Menyhárd, Dóra K.; Harvey, Jeremy N.; Oláh, J.

In: Chemistry - A European Journal, Vol. 24, No. 20, 06.04.2018, p. 5350-5358.

Research output: Contribution to journalArticle

Lábas, Anikó ; Menyhárd, Dóra K. ; Harvey, Jeremy N. ; Oláh, J. / First Principles Calculation of the Reaction Rates for Ligand Binding to Myoglobin : The Cases of NO and CO. In: Chemistry - A European Journal. 2018 ; Vol. 24, No. 20. pp. 5350-5358.
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