Photolyase is an enzyme that catalyses the photorepair of thymine dimers in UV damaged DNA by an electron transfer reaction [Park et al., 1995]. The electronic coupling between the lowest unoccupied molecular orbitals of the catalytic cofactor and a thymine dimer bound in the active site of the enzyme is examined in extended Hückel approximation. This method has been already used to study an internal electron transfer in photolyase [Cheung et al., 1999]. The bound configuration of the thymine dimer is predicted with the DOCK 4.0 program [Kuntz, 1992]. Thus a quantum and a molecular mechanical method are applied in combination.
It is found that in the configuration with the strongest electron transfer matrix element the docked thymine dimer is sitting deep in the catalytic site. This binding mode confirms the results of a recent mutagenesis study [Berg and Sancer, 1998]. Bound in this orientation the electronic coupling between the donor and the acceptor states is not direct, but indirect, with a part of the catalytic cofactor acting as an intermediate. The electron transfer mechanism utilizes the unusual conformation of this cofactor, a flavin adenine dinucleotide, in photolyases and the peculiar features of the docked orientation of the dimer.