Effect of Solvation on Electron Detachment and Excitation Energies of a Green Fluorescent Protein Chromophore Variant

Abstract

Hybrid quantum mechanics/molecular mechanics (QM/MM) is applied to the fluorinated green fluorescent protein (GFP) chromophore (DFHBDI) in its deprotonated form to understand the solvatochromic shifts in its vertical detachment energy (VDE) and vertical excitation energy (VEE). This variant of the GFP chromophore becomes fluorescent in an RNA environment and has a wide range of applications in biomedical and biochemical fields. From microsolvation studies, we benchmark (with respect to full QM) the accuracy of our QM/MM calculations with effective fragment potential (EFP) as the MM method of choice. We show that while the solvatochromic shift in the VEE is minimal (0.1 eV blue shift) and its polarization component is only 0.03 eV, the effect of the solvent on the VDE is quite large (3.85 eV). We also show by accurate calculations on the solvatochromic shift of the VDE that polarization accounts for ∼0.23 eV and therefore cannot be neglected. The effect of the counterions on the VDE of the deprotonated chromophore in solvation is studied in detail, and a charge-smearing scheme is suggested for charged chromophores.

An interaction energy driven biased sampling technique: A faster route to ionization spectra in condensed phase

“…Both electron attachment and detachment processes result in a change in the net charge of the chromophore and cause a significant redistribution of electron density. Therefore, IE and EA of a chromophore is expected to be significantly affected by the environment . For example, as illustrated in Ref.…”

“…However, due to the large number of degrees of freedom that need to be considered in condensed phases, a hybrid quantum mechanical/molecular mechanical (QM/MM) approach is required . A combined classical molecular dynamics (MD) and hybrid QM/MM approach has been documented as an accurate method for the estimation of spectral properties in the condensed phases . Furthermore, it has been noticed that point charge MM models of water, such as TIP3P, in the hybrid QM/MM calculations, are not adequate to predict the IEs accurately, as polarization is an important component of the solvatochromic shifts …”

“…Effective fragment potential (EFP) is a sophisticated polarizable MM method, and it has been benchmarked for the prediction of properties such as IEs using a hybrid QM/EFP formalism . EFP describes the discrete molecules as a combination of static multipole moments and induced dipole moments to include both accurate electrostatics (Coulomb) and polarization interactions.…”

“…The MD simulations are typically used to generate the different configurations mentioned above that follow a Boltzmann distribution. It has been noticed that a reasonably long simulation is required followed by the computation of the IEs over large number of configurations . The slow convergence of the average, as well as the spectral broadening is due to the extreme sensitivity of the IEs on the solvent environment, especially in polar solvents.…”

Multiscale Modelling:Hybrid Quantum Mechanics/Molecular Mechanics as an Example and some Recent Developments

“…Using this formalism, we have been able to accurately predict the ionization energies and excitation energies of biological systems such as DNA bases, GFP chromophores etc in solvation [27][28][29] .…”