Redox properties of cytochrome c: novel linear response and hybrid continuum-microscopic methodologies

Redox properties of yeast cytochrome c are estimated using molecular dynamics combined with a simple linear response approximation, as well as a hybrid continuum-molecular dynamics (COMD) approach. In both approaches, the free energy associated with an electrostatic perturbation (a redox electron) is separated into its relaxation and static (non-relaxation) components. The static component is calculated from the molecular dynamics simulation. The relaxation component is then calculated with a linear response approximation, either from the molecular dynamics, or from a separate continuum calculation. This latter hybrid approach exploits the relative robustness of continuum models for dealing with large perturbations, while avoiding some of their limitations. It is quite general, and could be applied for example to pKa calculations.