title: Calculation of the relative free energy of oxidation of Azurin at pH 5 and pH 9.
abstract: Free energy calculations are described for the small copper-containing redox protein Azurin from Pseudomonas aeruginosa. A thermodynamic cycle connecting the reduced and oxidized states at pH 5 and pH 9 is considered, allowing for an assessment of convergence in terms of hysteresis and cycle closure. Previously published thermodynamic integration (TI) data is compared to Hamiltonian replica exchange TI (RE-TI) simulations using different simulation setups. The effects of varying simulation length, initial structure, position restraints on particular atoms, and the strength of temperature coupling are studied. Although the overall simulation times are too short to observe an experimentally described peptide plane rotation, it is found that RE-TI simulations do stimulate the distribution of conformational changes over the relevant values of the TI coupling parameter λ. This results in significantly improved values for hysteresis and cycle closure when compared to regular TI.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich, ETH Zürich, Zürich CH-8093, Switzerland.
authors.forename: Denise
authors.initials: D
authors.lastname: Steiner
authors.forename: Chris
authors.initials: C
authors.lastname: Oostenbrink
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: van Gunsteren
mesh_terms: D001400:Azurin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010084:Oxidation-Reduction; D011550:Pseudomonas aeruginosa / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D001400:Azurin