title: Quantum Chemical Benchmark Studies of the Electronic Properties of the Green Fluorescent Protein Chromophore: 2. Cis-Trans Isomerization in Water.
abstract: We present quantum chemical calculations of the properties of the anionic form of the green fluorescent protein (GFP) chromophore that can be directly compared to the results of experimental measurements: the cis-trans isomerization energy profile in water. Calculations of the cis-trans chromophore isomerization pathway in the gas phase and in water reveal a problematic behavior of density functional theory and scaled opposite-spin-MP2 due to the multiconfigurational character of the wave function at twisted geometries. The solvent effects treated with the continuum solvation models, as well as with the water cluster model, are found to be important and can reduce the activation energy by more than 10 kcal/mol. Strong solvent effects are explained by the change in charge localization patterns along the isomerization coordinate. At the equilibrium, the negative charge is almost equally delocalized between the phenyl and imidazolin rings due to the interaction of two resonance structures, whereas at the transition state the charge is localized on the imidazolin moiety. Our best estimate of the barrier obtained in cluster calculations employing the effective fragment potential-based quantum mechanics/molecular mechanics method with the complete active space self-consistent field description of the chromophore augmented by perturbation theory correction and the TIP3P water model is 14.8 kcal/mol, which is in excellent agreement with the experimental value of 15.4 kcal/mol. This result helps to resolve previously reported disagreements between experimental measurements and theoretical estimates.
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California 90089, Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow 119991, Russia, and Institute of Biochemical Physics, Russian Academy of Sciences, Moscow 119334, Russia.
authors.forename: Igor
authors.initials: I
authors.lastname: Polyakov
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California 90089, Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow 119991, Russia, and Institute of Biochemical Physics, Russian Academy of Sciences, Moscow 119334, Russia.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Epifanovsky
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California 90089, Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow 119991, Russia, and Institute of Biochemical Physics, Russian Academy of Sciences, Moscow 119334, Russia.
authors.forename: Bella
authors.initials: B
authors.lastname: Grigorenko
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California 90089, Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow 119991, Russia, and Institute of Biochemical Physics, Russian Academy of Sciences, Moscow 119334, Russia.
authors.forename: Anna I
authors.initials: AI
authors.lastname: Krylov
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California 90089, Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow 119991, Russia, and Institute of Biochemical Physics, Russian Academy of Sciences, Moscow 119334, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Nemukhin