This study focuses on electron transfer in proteins using Molecular Dynamics (MD) simulations backed by analytical theory. Beginning as a test of the linear response approximation (LRA), the blue copper protein plastocyanin (PC) was used as a model for the energetics of proteins that transfer electrons in solution. MD trajectories of PC were used to calculate a time series of the vertical energy gap. Analysis of this data shows a breakdown in the LRA by finding the reorganization energy due to the variance in the energy gap is nearly an order of magnitude larger than the corresponding value from the Stokes shift. This lead to a phenomenological model that incorporates an observation time dependent reorganization energy and a frozen Stokes shift, providing a drastic lowering of the activation barrier of electron transfer with increasing observation time.

Following this work, the attention of the thesis turns toward the bacterial reaction center (RC), a protein with a charge separation reaction that occurs on the picosecond time-scale. Using both a non-polarizable and polarizable simulation protocol, the uncovered data shows that, although the reorganization energy is dependent on observation time, on this short time-scale the reorganization energy falls considerably while polarizable free energy surfaces of electron transfer appear funnel-shaped. Additionally, parameters from MD simulations of RC can be used with Matyushov's non-ergodic theory to fit relevant experimental data.

The RC data suggested a tie between the gigantic reorganization energy and the onset of increasing protein flexibility. This prompted a return to PC, where MD simulations show the breakdown in the LRA beginning in the temperature region near 200K, below which the statistics are largely Gaussian. Near 220 K, all reorganization energies show a spike, which nears 10 eV on the 10 nanosecond time-scale. Concurrently, the exponential relaxation time critically slows down, and the density of the water at the interface fluctuates wildly, driving the creation of a hydrophobic interface.

The thesis concludes with a protocol for the simulation of all systems mentioned in this study, as well as detailed presentation of a parallel algorithm developed to analyze such MD trajectories.