Photolyases use visible light, preferentially from the violet/blue end of the spectrum for DNA repair, and this phenomenon is known as photo reactivation. The photolyase mechanism is no longer working in humans and other placental mammals, relying instead on the less efficient nucleotide excision repair mechanism for DNA repair. During the three year EU-funded PINADBIO (First principles study of photoinduced non-adiabatic dynamics in DNA repair by photolyases) project, researchers explored novel and more accurate methodologies for the investigation of the force fields and dynamics of the repair process. More specifically, the team explored viable quantum dynamic and multi-configuration electronic structure methods to provide a physically sounded description of critical repair steps. The first step of the project was the design of an active site molecular model capable of describing the repair process while being small enough to be studied. Using the developed methodology, the researchers studied initial slow electron transfer in the cyclobutane pyrimidine dimer photolyase, which is a key step in the understanding of the efficiency of the repair process. In parallel, new methods have been developed to explore the electronic energy landscape in the nuclear coordinate space and to map the corresponding potential energy surfaces. Simulation of the quantum dynamics of a molecular system requires the construction of a model Hamiltonian. Indeed, simple parametrised Hamiltonian models were constructed by fitting the model over an important number of nuclear geometries. These models were used in combination with the non-equilibrium Fermi golden rule method to estimate the electron transfer time scale and then compared to experimental data. In conclusion, this new approach is promising for quantum statistics in general as it provides new perspectives for the treatment of environmental effects. It solves the unphysical behaviour of the quantum subsystem for any type of wave-function parametrisation.
Molecular models, DNA repair, photolyase, PINADBIO, quantum statistics