Membrane-bound molecular probes that fluoresce in response to a change in membrane voltage and produce photons whose color is highly sensitive to their environment, are exceedingly useful in studies monitoring a variety of excitable cell activities. Such factors include the polarity of solvent, specific lipid composition of membrane, and ionic concentration. By simulating such systems with molecular dynamics, switching between the ground and excited state force fields of the given probe, each of these characteristics can be investigated individually to determine how changing each would affect the observed photon color. The force field parameterization of the probes themselves is accomplished with General Automated Atomic Model Parameterization (GAAMP) software, which improves upon the results of either CGenff or Antechamber with additional quantum mechanical calculations. These generated force fields treat induced polarization explicitly with the inclusion of drude particles assigned to each heavy atom. In such a treatment, each non-hydrogen atom has its charge split between a point at its nucleus and a massless particle tethered to it by a harmonic spring. This allows for greater responsiveness to electric field and a more accurate representation of a molecule's polar properties. TD-DFT calculations were incorporated into GAAMP to allow this treatment to be extended to the excited states of molecules, and additional efforts are being made to include CASSCF options as well to accommodate structures not accurately handled by TD-DFT.

Modeling voltage-sensitive fluorescing membrane-bound probes using GAAMP parameterization to investigate their properties

2019 Spring National Meeting

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