Nonadiabatic QM/MM Simulations of Fast Charge Transfer in Escherichia coli DNA Photolyase

Abstract

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.

Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor

“…The limited evidence available suggests that the Trp radical is mostly localized on W C (i.e., k ET ≫ k 0 ET ) and that k 0 ET may be fast enough to allow reversible electron hopping from and to W B during the lifetime of RP1 (26,34,35). Using center-to-center FAD-Trp separations calculated (36) from the X-ray structure of AtCry (37) (1.32 nm for RP0 and 1.90 nm for RP1), the interradical electron exchange interactions have been estimated (36) as jJ RP0 j ≈ 10 3 mT and jJ RP1 j ≈ 10 −1 mT.…”

A hybrid approach to simulation of electron transfer in complex molecular systems

“…This is the case with E. coli DNA photolyase [123], in which the photo-activation process proceeds via a sequential transfer of a hole from the flavin adenine dinucleotide (FAD) cofactor via two tryptophan side chains (Trp1 and Trp2) to a terminal tryptophan (Trp3) at the surface of the protein [124] ( figure 6). The hole transfer in the subsystem composed of three tryptophan side chains was considered in our work [34], and the main findings will be presented in this review because another type of energy relations in a CT system is observed here. The fundamental difference between the charge transfer in DNA and in this enzyme concerns the properties of the molecular environment rather than the charge-carrying molecular fragments themselves.…”

Progress and challenges in simulating and understanding electron transfer in proteins

“…The time-dependent Schrödinger equation is solved for the electronic part and Ehrenfest (mean field) algorithms are then applied to propagate the electronic-nuclear dynamics. This algorithm has been applied to investigate multiple-site charge migrations in DNA [39], in DNA photolyases [40,41] and more recently in a plant cryptochrome [42]. In photolyase and in plant cryptochromes, the protein encapsulates a flavin cofactor which can be reduced, after electronic excitation, by a nearby tryptophan residue (Fig.…”