Bathochromic Shift in Green Fluorescent Protein: A Puzzle for QM/MM Approaches
Bathochromic Shift in Green Fluorescent Protein: A Puzzle for QM/MM Approaches
复制标题
DOI：
10.1021/ct200704k
复制
发表时间：
2012-01-01
影响因子：
5.5
通讯作者：
Sinicropi, Adalgisa
中科院分区：
文献类型：
--
作者：
Filippi, Claudia;Buda, Francesco;Sinicropi, Adalgisa
我们提出了一个广泛的调查的垂直激发的阴离子和中性形式的野生型绿色荧光蛋白使用含时密度泛函理论（TDDFT），多构型微扰理论（CASPT 2），和量子蒙特卡罗（QMC）方法在量子力学/分子力学（QM/MM）计划。蛋白质模型通过基于DFT的室温QM/MM分子动力学模拟构建，并且代表发色团蛋白质复合物的平均构型。我们通过使用扩展的QM区域、不同的不可极化力场以及使用CASPT 2方法的部分重新优化进行模拟，彻底验证了我们结构的可靠性。当计算的激发，我们发现，波函数以及密度泛函理论方法与远程校正泛函同意在气相中的溶液实验的外推，但未能再现的红移的蛋白质，这应该是特别重要的中性情况下。特别是，虽然所有方法都正确预测了蛋白质的阴离子和中性形式之间的吸收偏移，但理论吸收最大值的位置明显蓝移，并且过于接近气相值。这些结果表明，无论是固有的限制nonpolarizable力场嵌入在计算的激发或需要探索替代质子化状态的氨基酸在附近的chomophore。
We present an extensive investigation of the vertical excitations of the anionic and neutral forms of wild-type green fluorescent protein using time-dependent density functional theory (TDDFT), multiconfigurational perturbation theory (CASPT2), and quantum Monte Carlo (QMC) methods within a quantum mechanics/molecular mechanics (QM/MM) scheme. The protein models are constructed via room-temperature QM/MM molecular dynamics simulations based on DFT and are representative of an average configuration of the chromophore protein complex. We thoroughly verify the reliability of our structures through simulations with an extended QM region, different nonpolarizable force fields, as well as partial reoptimization with the CASPT2 approach. When computing the excitations, we find that wave function as well as density functional theory methods with long-range corrected functionals agree in the gas phase with the extrapolation of solution experiments but fail in reproducing the bathochromic shift in the protein, which should be particularly significant in the neutral case. In particular, while all methods correctly predict a shift in the absorption between the anionic and neutral forms of the protein, the location of the theoretical absorption maxima is significantly blue-shifted and too close to the gas-phase values. These results point to either an intrinsic limitation of nonpolarizable force-field embedding in the computation of the excitations or to the need to explore alternative protonation states of amino acids in the close vicinity of the chomophore.