Simulating biological charge transfer: Continuum dielectric theory or molecular dynamics?

We study the thermodynamic parameters of Marcus's theory of charge transfer, the driving forces and the reorganization energies, using two widely applied approaches to bioenergetic problems that seem to be radically different: continuum dielectric theory via a numerical solution of Poisson's equation, and the thermodynamic integration approach based upon classical Newtonian molecular dynamics, as perfomed by Na et al., PCCP 19, 18,938 (2017). With application to a nitrite reductase NrfHA protein heterodimer, we obtain an excellent agreement between the respective driving forces with an r.m.s. deviation of 1.7 kcal/mol, and a lower limit to the reorganization energies. The computational methods turn out to be mutually supportive: molecular dynamics can be used to determine the parameters of a dielectric theory computation, which on the other hand can be used to properly rescale the reorganization energies and partition them into aqueous and protein contributions. In addition, we use the electrostatic approach to study the influence of Ca2+ ions on the free energy landscape of charge transfer.