title: Chromophore-protein coupling beyond nonpolarizable models: understanding absorption in green fluorescent protein.
abstract: The nature of the coupling of the photoexcited chromophore with the environment in a prototypical system like green fluorescent protein (GFP) is to date not understood, and its description still defies state-of-the-art multiscale approaches. To identify which theoretical framework of the chromophore-protein complex can realistically capture its essence, we employ here a variety of electronic-structure methods, namely, time-dependent density functional theory (TD-DFT), multireference perturbation theory (NEVPT2 and CASPT2), and quantum Monte Carlo (QMC) in combination with static point charges (QM/MM), DFT embedding (QM/DFT), and classical polarizable embedding through induced dipoles (QM/MMpol). Since structural modifications can significantly affect the photophysics of GFP, we also account for thermal fluctuations through extensive molecular dynamics simulations. We find that a treatment of the protein through static point charges leads to significantly blue-shifted excitation energies and that including thermal fluctuations does not cure the coarseness of the MM description. While TDDFT calculations on large cluster models indicate the need of a responsive protein, this response is not simply electrostatic: An improved description of the protein in the ground state or in response to the excitation of the chromophore via ground-state or state-specific DFT and MMpol embedding does not significantly modify the results obtained with static point charges. Through the use of QM/MMpol in a linear response formulation, a different picture in fact emerges in which the main environment response to the chromophore excitation is the one coupling the transition density and the corresponding induced dipoles. Such interaction leads to significant red-shifts and a satisfactory agreement with full QM cluster calculations at the same level of theory. Our findings demonstrate that, ultimately, faithfully capturing the effects of the environment in GFP requires a quantum treatment of large photoexcited regions but that a QM/classical model can be a useful approximation when extended beyond the electrostatic-only formulation.
authors.affiliation: MESA+ Institute for Nanotechnology, University of Twente , P.O. Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: Csaba
authors.initials: C
authors.lastname: Daday
authors.affiliation: Departament de Fisicoquı́mica, Facultat de Farmàcia, Universitat de Barcelona , Av. Joan XXIII, s/n 08028, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Curutchet
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena , Via A. Moro, 2, 53100 Siena, Italy.
authors.forename: Adalgisa
authors.initials: A
authors.lastname: Sinicropi
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, Università di Pisa , Via Giuseppe Moruzzi 3, 56124 Pisa, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mennucci
authors.affiliation: MESA+ Institute for Nanotechnology, University of Twente , P.O. Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: Claudia
authors.initials: C
authors.lastname: Filippi
mesh_terms: D065966:Absorption, Physicochemical; D004583:Electrons; D049452:Green Fluorescent Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009010:Monte Carlo Method; D011789:Quantum Theory; D013997:Time Factors
chemical_list: D049452:Green Fluorescent Proteins