Flavin Charge Transfer Transitions Assist DNA Photolyase Electron Transfer

This contribution describes molecular dynamics, semi-empirical and ab-initio studies of the primary photo-induced electron transfer reaction in DNA photolyase. DNA photolyases are FADH−-containing proteins that repair UV-damaged DNA by photo-induced electron transfer. A DNA photolyase recognizes and binds to cyclobutatne pyrimidine dimer lesions of DNA. The protein repairs a bound lesion by transferring an electron to the lesion from FADH−, upon photo-excitation of FADH− with 350–450 nm light. We compute the lowest singlet excited states of FADH− in DNA photolyase using INDO/S configuration interaction, time-dependent density-functional, and time-dependent Hartree-Fock methods. The calculations identify the lowest singlet excited state of FADH− that is populated after photo-excitation and that acts as the electron donor. For this donor state we compute conformationally-averaged tunneling matrix elements to empty electron- acceptor states of a thymine dimer bound to photolyase. The conformational averaging involves different FADH− - thymine dimer confromations obtained from molecular dynamics simulations of the solvated protein with a thymine dimer docked in its active site. The tunneling matrix element computations use INDO/S-level Green’s function, energy splitting, and Generalized Mulliken-Hush methods. These calculations indicate that photo-excitation of FADH− causes a π → π* charge-transfer transition that shifts electron density to the side of the flavin isoalloxazine ring that is adjacent to the docked thymine dimer. This shift in electron density enhances the FADH− - to - dimer electronic coupling, thus inducing rapid electron transfer

Photoselected electron transfer pathways in DNA photolyase

Cyclobutane dimer photolyases are proteins that bind to UV-damaged DNA containing cyclobutane pyrimidine dimer lesions. They repair these lesions by photo-induced electron transfer. The electron donor cofactor of a photolyase is a two-electron-reduced flavin adenine dinucleotide (FADH(−)). When FADH(−) is photo-excited, it transfers an electron from an excited π → π* singlet state to the pyrimidine dimer lesion of DNA. We compute the lowest excited singlet states of FADH(−) using ab initio (time-dependent density functional theory and time-dependent Hartree–Fock), and semiempirical (INDO/S configuration interaction) methods. The calculations show that the two lowest π → π* singlet states of FADH(−) are localized on the side of the flavin ring that is proximal to the dimer lesion of DNA. For the lowest-energy donor excited state of FADH(−), we compute the conformationally averaged electronic coupling to acceptor states of the thymine dimer. The coupling calculations are performed at the INDO/S level, on donor–acceptor cofactor conformations obtained from molecular dynamics simulations of the solvated protein with a thymine dimer docked in its active site. These calculations demonstrate that the localization of the (1)FADH(−)* donor state on the flavin ring enhances the electronic coupling between the flavin and the dimer by permitting shorter electron-transfer pathways to the dimer that have single through-space jumps. Therefore, in photolyase, the photo-excitation itself enhances the electron transfer rate by moving the electron towards the dimer

Chiral control of current transfer in molecules

Abstract Electron transmission through chiral molecules induced by circularly polarized light can be very different for mirror image structures. This behaviour is described in terms of current transfer: the transfer of both charge and momentum. We review recent theoretical developments on the theory of current transfer and discuss related experimental studies of electron transmission through chiral molecular structures adsorbed on surfaces.

Biological Charge Transfer Via Flickering Resonance

Biological electron-transfer (ET) reactions are typically described in the framework of coherent two-state electron tunneling or multistep hopping. However, these ET reactions may involve multiple redox cofactors in van der Waals contact with each other and with vibronic broadenings on the same scale as the energy gaps among the species. In this regime, fluctuations of the molecular structures and of the medium can produce transient energy level matching among multiple electronic states. This transient degeneracy, or flickering electronic resonance among states, is found to support coherent (ballistic) charge transfer. Importantly, ET rates arising from a flickering resonance (FR) mechanism will decay exponentially with distance because the probability of energy matching multiple states is multiplicative. The distance dependence of FR transport thus mimics the exponential decay that is usually associated with electron tunneling, although FR transport involves real carrier population on the bridge and is not a tunneling phenomenon. Likely candidates for FR transport are macromolecules with ET groups in van der Waals contact: DNA, bacterial nanowires, multiheme proteins, strongly coupled porphyrin arrays, and proteins with closely packed redox-active residues. The theory developed here is used to analyze DNA charge-transfer kinetics, and we find that charge-transfer distances up to three to four bases may be accounted for with this mechanism. Thus, the observed rapid (exponential) distance dependence of DNA ET rates over distances of ≲15 Å does not necessarily prove a tunneling mechanism