On the Driving Force of the Excited-State Proton Shuttle
in the Green Fluorescent Protein: A Time-Dependent Density Functional
Theory (TD-DFT) Study of the Intrinsic Reaction Path
posted on 2016-08-29, 00:00authored byAlessio Petrone, Paola Cimino, Greta Donati, Hrant
P. Hratchian, Michael J. Frisch, Nadia Rega
We
simulated the intrinsic reaction path of the Green Fluorescent
Protein (GFP) proton shuttle in both the ground state (S0) and first singlet excited state (S1), accounting for
the main energetic and steric effects of the protein in a convenient
model including the chromophore, the crystallographic water, and the
residues directly involved in the proton transfer event. We adopted
density functional theory (DFT) and time-dependent density functional
theory (TD-DFT) levels to define the potential energy surfaces of
the two electronic states, and we compared results obtained by the
Damped Velocity Verlet and the Hessian-based Predictor–Corrector
integrators of the intrinsic reaction coordinate, which gave a comparable
and consistent picture of the mechanism. We show that, at S1, the GFP proton transfer becomes favored, with respect to S0, as suggested by the experimental evidence. As an important
finding, this change is strictly related to the rearrangement of the
hydrogen bond network composing the reaction path, which, in S1, relaxes to a tighter and planar configuration, as a consequence
of the photoinduced relaxation in the GFP chromophore structure, thus
prompting more effectively for the proton shuttle. Therefore, we give
an unprecedented direct proof of the key role played by the photoinduced
structural relaxation of the GFP on the chromophore photoacidity,
validating, in particular, the hypothesis of Fang and co-workers [Nature2009, 462, 200].