Free energies for biological electron transfer from QM/MM calculation: method, application and critical assessment†
Computer simulations of biological electron transfer reactions are reviewed with a focus on the calculation of reaction free energy (driving force) and reorganization free energy. Then a mixed quantum mechanical/molecular mechanical (QM/MM) approach is described which is designed for computation of these quantities for pure electron transfer reactions with large donor–acceptor separation distances. The method is applied to intra-protein electron transfer in Ru(bpy)2(im)His33 cytochrome c and the results compared to experimental data. Several modeling aspects which are important for successful calculation of free energies with QM/MM are discussed in detail.