Theoretical study of excitation energy transfer in DNA photolyase.

Photolyase (PL) is a DNA repair enzyme which splits UV light-induced thymine dimers on DNA by an electron transfer reaction occurring between the photoactivated FADH(-) cofactor and the DNA dimer in the DNA/PL complex. The crystal structure of the DNA/photolyase complex from Anacystis nidulans has been solved. Here, using the experimental crystal structure, we re-examine the details of the repair electron transfer reaction and address the question of energy transfer from the antenna HDF to the redox active FADH(-) cofactor. The photoactivation of FADH(-) immediately preceding the electron transfer is a key step in the repair mechanism that is largely left unexamined theoretically. An important butterfly thermal motion of flavin is identified in ab initio calculations; we propose its role in the back electron transfer from DNA to photolyase. Molecular dynamics simulation of the whole protein/DNA complex is carried out to obtain relevant cofactor conformations for ZINDO/S spectroscopic absorption and fluorescence calculations. We find that significant thermal broadening of the spectral lines, due to protein dynamics, as well as the alignment of the donor HDF and the acceptor FADH(-) transition dipole moments both contribute to the efficiency of energy transfer. The geometric factor of Förster's dipolar coupling is calculated to be 1.82, a large increase from the experimentally estimated 0.67. Using Förster's mechanism, we find that the energy transfer occurs with remarkable efficiency, comparable with the experimentally determined value of 98%.