Electrostatic effects in the Brownian dynamics of association and orientation of heme proteins

The Brownian dynamics (BD) method is applied to the diffusional association of electron-transfer proteins cytochrome c (CYTC) and cytochrome c peroxidase (CYP). They examine the role of protein electrostatic charge distribution and solvent mediation in the facilitation of protein-protein docking prior to the electron-transfer step. Accurate interaction potentials are computed by iterating the linearized Poisson-Boltzmann equation around the larger protein CYP. The lower dielectric constant inside proteins and their irregular surface topography are taken into account. Realistic criteria for determining the successful docking of the proteins are based on a combination of mutual orientation of heme planes and heme edge-to-edge distance. The proteins successfully meet the most stringent of these criteria in two distinct regions of relative separation space which coincide with two electrostatically attractive regions. The existence of a large ensemble of electrostatically stable encounter complexes seemingly with acceptable geometric requirements for electron transfer is observed rather than a single dominant complex. The reaction criteria matching the experimental association rate is the case in which the heme edge distance is inside 20 A and the heme planes are coparallel to within 60/sup 0/. Ionic strength dependence of the association rate for this case agrees with that observed in experiment in the physiological regime. Association at random heme plane orientation results in a rate constant which is almost twice as large as that from experiment.