In this report, we study the photoactivation process in Escherichia coli DNA photolyase, involving long-range electron transport along a conserved chain of Trp residues between the protein surface and the flavin adenine dinucleotide (FAD) cofactor. Fully coupled nonadiabatic (Ehrenfest) quantum mechanics/molecular mechanics (QM/MM) simulations allow us to follow the time evolution of charge distributions over the natural time scale of multiple charge transfer events and conduct rigorous statistical analysis. Charge transfer rates in excellent agreement with experimental data are obtained without the need for any system-specific parametrization. The simulations are shown to provide a more detailed picture of electron transfer than a classical analysis of Marcus parameters. The protein and solvent both strongly influence the localization and transport properties of a positive charge, but the directionality of the process is mainly caused by solvent polarization. The time scales of charge movement, delocalization, protein relaxation and solvent reorganization overlap and lead to nonequilibrium reaction conditions. All these contributions are explicitly considered and fully resolved in the model used and provide an intricate picture of multistep biochemical electron transfer in a flexible, heterogeneous environment.

We investigate in detail the charge transport characteristics of DNA wires with various sequences and lengths in the presence of solvent. Our approach combines large-scale quantum/classical molecular dynamics (MD) simulations with transport calculations based on Landauer theory. The quantum mechanical transmission function of the wire is calculated along MD trajectories and thus encodes the influence of dynamical disorder arising from the environment (water, backbone, counterions) and from the internal base dynamics. We show that the correlated fluctuations of the base pair dynamics are crucial in determining the transport properties of the wire and that the effect of fluctuations can be quite different for sequences with low and high static disorders (differences in base ionization potentials). As a result, in structures with high static disorder as is the case of the studied Dickerson dodecamer, the weight of high-transmissive structures increases due to dynamical fluctuations and so does the calculated average transmission. Our analysis further supports the basic intuition of charge-transfer active conformations as proposed by Barton et al. [J. Am. Chem. Soc. 126, 11471 (2004)]. However, not DNA conformations with good stacking contacts leading to large interbase hopping values are necessarily the most important, but rather those where the average fluctuation of ionization potentials along the base stack is small. The reason behind this is that the ensemble of conformations leads to average electronic couplings, which are large enough for sufficient transmission. On the other hand, the alignment of onsite energies is the critical parameter which gates the charge transport.

Abstract. Charge transport through a short DNA oligomer (Dickerson dodecamer (DD)) in the presence of structural fluctuations is investigated using a hybrid computational methodology based on a combination of quantum mechanical electronic structure calculations and classical molecular dynamics (MD) simulations with a model Hamiltonian approach. Based on a fragment orbital description, the DNA electronic structure can be coarse-grained in a very efficient way. The influence of dynamical fluctuations, arising either from the solvent fluctuations or from base-pair vibrational modes, can be taken into account in a straightforward way through the time series of the effective DNA electronic parameters, evaluated at snapshots along the MD trajectory. We show that charge transport can be promoted through the coupling to solvent fluctuations, which gate the on-site energies along the DNA wire.

Molecules in junctions often fluctuate considerably, especially when subject to the influence of solvent molecules. These fluctuations in site energies and couplings can be sampled, for example, by using molecular dynamics simulations, and can lead to incoherent effects in charge transport. To this end, a popular snapshot-averaged Landauer approach is compared to a time-dependent Green's function scheme. Since sequential transport dominates in systems with rapidly varying bridges, schemes not taking the time order of conformations into account, such as the Landauer approach, are inappropriate.

We study fast hole transfer events in E. coli DNA photolyase, a key step in the photoactivation process, using a multiscale computational method that combines nonadiabatic propagation schemes and linear-scaling quantum chemical methods with molecular mechanics force fields. This scheme allows us to follow the time-dependent evolution of the electron hole in an unbiased fashion; that is, no assumptions about hole wave function localization, time scale separation, or adiabaticity of the process have to be made beforehand. DNA photolyase facilitates an efficient long-range charge transport between its flavin adenine dinucleotide (FAD) cofactor and the protein surface via a chain of evolutionary conserved Trp residues on the sub-nanosecond time scale despite the existence of multiple potential trap states. By including a large number of aromatic residues along the charge transfer pathway into the quantum description, we are able to identify the main pathway among alternative possible routes. The simulations show that charge transfer, which is extremely fast in this protein, occurs on the same time scale as the protein response to the electrostatic changes; that is, time-scale separation as often presupposed in charge transfer studies seems to be inappropriate for this system. Therefore, coupled equations of motion, which propagate electrons and nuclei simultaneously, appear to be necessary. The applied computational model is shown to capture the essentials of the reaction kinetics and thermodynamics while allowing direct simulations of charge transfer events on their natural time scale.