Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods.

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We have used combined quantum mechanical and molecular mechanical free-energy perturbation methods in combination with explicit solvent simulations to study the reaction mechanism of the multicopper oxidases, in particular, the regeneration of the reduced state from the native intermediate. For 52 putative states of the trinuclear copper cluster, differing in the oxidation states of the copper ions and the protonation states of water- and O2-derived ligands, we have studied redox potentials, acidity constants, isomerization reactions, as well as water- and O2 binding reactions. Thereby, we can propose a full reaction mechanism of the multicopper oxidases with atomic detail. We also show that the two copper sites in the protein communicate so that redox potentials and acidity constants of one site are affected by up to 0.2 V or 3 pKa units by a change in the oxidation state of the other site.


  • Jilai Li
  • Maryam Farrokhnia
  • Lubomir Rulisek
  • Ulf Ryde
External organisations
  • Jilin University
  • Bushehr University of Medical Sciences
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Physical Chemistry
Original languageEnglish
Pages (from-to)8268-8284
JournalThe Journal of Physical Chemistry Part B
Issue number26
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)

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