Binding of pyrimidine model dimers to the photolyase enzyme: A molecular dynamics study

Molecular dynamics simulations have been carried out to study structural aspects of the photo repair mechanism of DNA photolyase. In particular, we investigated the docking and binding of bare and dressed model pyrimidine dimers, U〈〉T and dU〈p〉dT, respectively, in the enzyme pocket. These dimers, which split after photoinduced electron transfer, are essentially inflexible in the gas phase, in water, and inside the enzyme pocket. Details of the dimer docking and the binding inside the pocket are presented and the influence of the desoxyribose and phosphate link on the dimer docking are discussed. The minimum van der Waals distances for the electron transfer between the electron donor FADH^- and the accepting dimers are found to be about 5 Å for U〈〉T and about 9 Å for dU〈p〉dT. Analysis of the structure of the dimer models and their orientation in the enzyme pocket as well as the orientation of the FADH^- donor suggests that indirect electron transfer to the dimer may prevail.