Modeling Fluorescence Properties of Voltage-Sensitive Probes in Solvent and Embedded in Membrane Using Molecular Dynamics

Voltage-sensitive probes inserted into membranes can be used to report back changes to their immediate environment, especially in regards to the membrane potential, polarity, ion concentration and membrane composition. Experimentally, the relative changes in the color of the fluoresced photons of voltage-sensitive probes can even be used to help track signal transmission across neurons in vivo. However due to the sensitivity of these probes, there are many overlapping contributing factors to the exact color change, making it difficult to draw quantitative conclusions from studies in different systems. In order to investigate the degree to which different characteristics of a system contribute to the observed fluorescence changes of a probe molecule, atomic models have been developed. Rigorous force fields that treat induced polarization explicitly were created for the ground and excited state of the molecules of interest. Based on the Franck-Condon principle, which generally states that electronic transitions are instantaneous as compared to any nuclear movements, the computational representation of the electronic component of excitation and emission is as simple as switching force field parameters for the probe molecule creating the Franck-Condon state. The intramolecular relaxation and surrounding solvent fluctuations can then be monitored in molecular dynamic simulations immediately after switching the state of the molecule. Considering the significance of the change in polarity for these probe molecules, parameters were developed for both a typical nonpolarizable force field and a polarizable Drude force field. First, the probe was simulated in a series of solvents with varying polarity, and second, the probe was simulated in a simple DPPC membrane in the presence of an applied transmembrane potential.