Parameterization of the prosthetic redox centers of the bacterial cytochrome bc1 complex for atomistic molecular dynamics simulations

Cytochrome (cyt) bc1 is a multi-subunit membrane protein complex that is a vital component of the respiratory and photosynthetic electron transfer chains both in bacteria and eukaryotes. Although the complex’s dimer structure has been solved using X-ray crystallography, it has not yet been studied in large-scale classical molecular dynamics (MD) simulations. In part, this is due to lack of suitable force field parameters, centered atomic point charges in particular, for the complex’s prosthetic redox centers. Accurate redox center charges are needed to depict realistically the inter-molecular interactions at different redox stages of the cytbc1 complex. Accordingly, here we present high-precision atomic point charges for the metal centers of the cyt bc1 complex of Rhodobacter capsulatus derived from extensive density functional theory calculations, fitted using the restrained electrostatic potential methodology and combined with the CHARMM force field parameters. We also provide the Hartree–Fock charges for all substrate forms (quinol, quinone, and semiquinone) and the inhibitors antimycin and stigmatellin of the bacterial bc1 complex. The accuracy of the parameterization scheme was verified by running a 200-ns MD simulation encompassing the entire cyt bc1 complex embedded in a lipid bilayer and solvated with explicit water. The results indicate that these meticulously derived parameters are ready for running extensive MD simulations encompassing all biologically relevant stages of the cyt bc1 complex reaction cycle.