Steered molecular dynamics simulation of the rieske subunit motion in the cytochrome bc(1) complex

Crystallographic structures of the mitochondrial ubiquinol/cytochrome c oxi doreductase (cytochrome bc(1) complex) suggest that the mechanism of quinol oxidation by the bc(1) complex involves a substantial movement of the solu ble head of the Rieske iron-sulfur protein (ISP) between reaction domains i n cytochrome b and cytochrome c(1) subunits. In this paper we report the re sults of steered molecular dynamics simulations inducing, through an applie d torque within 1 ns, a 56 degrees rotation of the soluble domain of ISP. F or this purpose, a solvated structure of the bc(1) complex in a phospholipi d bilayer (a total of 206,720 atoms) was constructed. A subset of 91,061 at oms was actually simulated with 45,131 moving atoms. Point charge distribut ions for the force field parametrization of heme groups and the Fe2S2 clust er of the Rieske protein included in the simulated complex were determined. The simulations showed that rotation of the soluble domain of ISP is actua lly feasible. Several metastable conformations of the ISP during its rotati on were identified and the interactions stabilizing the initial, final, and intermediate positions of the soluble head of the ISP domain were characte rized. A pathway for proton conduction from the Q(o) site to the solvent vi a a water channel has been identified.