title: The Q-Cycle Mechanism of the bc1Complex: A Biologist's Perspective on Atomistic Studies.
abstract: The Q-cycle mechanism of the bc1complex is now well enough understood to allow application of advanced computational approaches to the study of atomistic processes. In addition to the main features of the mechanism, these include control and gating of the bifurcated reaction at the Qo-site, through which generation of damaging reactive oxygen species is minimized. We report a new molecular dynamics model of the Rhodobacter sphaeroides bc1complex implemented in a native membrane, and constructed so as to eliminate blemishes apparent in earlier Rhodobacter models. Unconstrained MD simulations after equilibration with ubiquinol and ubiquinone respectively at Qo- and Qi-sites show that substrate binding configurations at both sites are different in important details from earlier models. We also demonstrate a new Qo-site intermediate, formed in the sub-ms time range, in which semiquinone remains complexed with the reduced iron sulfur protein. We discuss this, and a spring-loaded mechanism for modulating interactions of the iron sulfur protein with occupants of the Qo-site, in the context of control and gating roles. Such atomistic features of the mechanism can usefully be explored through simulation, but we stress the importance of constraints from physical chemistry and biology, both in setting up a simulation and in interpreting results.
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign , 419 Roger Adams Lab, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.|Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign , 179 Loomis, 1110 West Green Street, Urbana, Illinois 61801, United States.
authors.forename: Antony R
authors.identifier: 0000-0003-3211-1349
authors.initials: AR
authors.lastname: Crofts
authors.affiliation: Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign , 179 Loomis, 1110 West Green Street, Urbana, Illinois 61801, United States.
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Rose
authors.affiliation: Department of Biochemistry, University of Illinois at Urbana-Champaign , 419 Roger Adams Lab, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Burton
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Amit V
authors.initials: AV
authors.lastname: Desai
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Paul J A
authors.identifier: 0000-0001-7348-0381
authors.initials: PJA
authors.lastname: Kenis
authors.affiliation: Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign , 1008 West Hazelwood Drive, Urbana, Illinois 61801, United States.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Dikanov
mesh_terms: D014450:Electron Transport Complex III / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D012242:Rhodobacter sphaeroides / Q000201:enzymology*
chemical_list: D014450:Electron Transport Complex III