Electron Transfer-Induced Active Site Structural Relaxation in 64-Photolyase of .

While catalytic electron flow and photoreactivation of CPD-photolyases are increasingly understood, the microscopic details of the 64-photolyase repair mechanism are perpetually debated. Here, we investigate in long-time (μs) molecular dynamics simulations combined with extensive quantum mechanical/molecular mechanical (QM/MM) simulations the primary electron transfer (ET) reactions in 64-photolyase of (). The characterization of the relative energetics of locally excited and charge separated states in the (6-4) photoproduct enzyme repair complex reveals a charge-separated state involving the adenine moiety of the FADH cofactor that facilitates reduction of the photoproduct.