How does the protein environment optimize the thermodynamics of thiol sulfenylation? Insights from model systems to QM/MM calculations on human 2-Cys peroxiredoxin

Julianna Oláh, Laura Van Bergen, Frank De Proft, Goedele Roos

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9 Citations (Scopus)


Protein thiol/sulfenic acid oxidation potentials provide a tool to select specific oxidation agents, but are experimentally difficult to obtain. Here, insights into the thiol sulfenylation thermodynamics are obtained from model calculations on small systems and from a quantum mechanics/molecular mechanics (QM/MM) analysis on human 2-Cys peroxiredoxin thioredoxin peroxidase B (Tpx-B). To study thiol sulfenylation in Tpx-B, our recently developed computational method to determine reduction potentials relatively compared to a reference system and based on reaction energies reduction potential from electronic energies is updated. Tpx-B forms a sulfenic acid (R-SO-) on one of its active site cysteines during reactive oxygen scavenging. The observed effect of the conserved active site residues is consistent with the observed hydrogen bond interactions in the QM/MM optimized Tpx-B structures and with free energy calculations on small model systems. The ligand effect could be linked to the complexation energies of ligand L with CH3S- and CH3SO-. Compared to QM only calculations on Tpx-Bs active site, the QM/MM calculations give an improved understanding of sulfenylation thermodynamics by showing that other residues from the protein environment other than the active site residues can play an important role.

Original languageEnglish
Pages (from-to)584-596
Number of pages13
JournalJournal of Biomolecular Structure and Dynamics
Issue number3
Publication statusPublished - Mar 4 2015



  • Ligand effect
  • Peroxiredoxin
  • QM/MM
  • Redox chemistry
  • Sulfenylation

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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