title: The reversible opening of water channels in cytochrome c modulates the heme iron reduction potential.
abstract: Dynamic protein-solvent interactions are fundamental for life processes, but their investigation is still experimentally very demanding. Molecular dynamics simulations up to hundreds of nanoseconds can bring to light unexpected events even for extensively studied biomolecules. This paper reports a combined computational/experimental approach that reveals the reversible opening of two distinct fluctuating cavities in Saccharomyces cerevisiae iso-1-cytochrome c. Both channels allow water access to the heme center. By means of a mixed quantum mechanics/molecular dynamics (QM/MD) theoretical approach, the perturbed matrix method (PMM), that allows to reach long simulation times, changes in the reduction potential of the heme Fe(3+)/Fe(2+) couple induced by the opening of each cavity are calculated. Shifts of the reduction potential upon changes in the hydration of the heme propionates are observed. These variations are relatively small but significant and could therefore represent a tool developed by cytochrome c for the solvent driven, fine-tuning of its redox functionality.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, 41125, Modena, Italy.
authors.forename: Carlo Augusto
authors.initials: CA
authors.lastname: Bortolotti
authors.forename: Andrea
authors.initials: A
authors.lastname: Amadei
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aschi
authors.forename: Marco
authors.initials: M
authors.lastname: Borsari
authors.forename: Stefano
authors.initials: S
authors.lastname: Corni
authors.forename: Marco
authors.initials: M
authors.lastname: Sola
authors.forename: Isabella
authors.initials: I
authors.lastname: Daidone
mesh_terms: D003575:Cytochromes c1 / Q000737:chemistry* / Q000378:metabolism; D006418:Heme / Q000737:chemistry* / Q000378:metabolism; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010084:Oxidation-Reduction; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D014867:Water / Q000737:chemistry* / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D014867:Water; D006418:Heme; D003575:Cytochromes c1; D007501:Iron