Quantitative prediction of spectral properties of polarity sensitive dyes using a MD/QM approach
Date
2020
Authors
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Publisher
University of Delaware
Abstract
The cell membrane is spatially heterogeneous, mostly in a fluid state, and composed of hundreds of different lipid types and proteins. Based on the composition and temperature, the lipids on cell membranes are packed into different kinds of phases, namely the gel phase, liquid-ordered phase, and liquid disordered phase. Polarity sensitive dyes such as Laurdan and Prodan, interrogate different lipid phases as the emission spectrum is red-shifted in the less dense liquid disordered phase compared to more dense gel or liquid-ordered phase. The shift in emission occurs because of the dipolar relaxation of solvents molecules present in the vicinity of the chromophore. ☐ An MD/QM approach is developed in which (i) the local environment is sampled by classical molecular dynamics (MD) simulation of the dye, (ii) the electronically excited state of Laurdan/Prodan is predicted using numerical quantum mechanics (QM), (iii) the environment around the excited dye is iteratively relaxed by MD coupled with the evolution of the excited state, and (iv) the emission properties are predicted by QM. The QM calculation is performed using many-body Green’s function approach within GW approximation. The Bethe-Salpeter equation is solved to obtain coupled electron-hole excitation, and the environment is modeled as fixed point charges sampled from MD simulation. This combination of methods is referred to below as MD/GW-BSE. ☐ The simulation results of MD/GW-BSE calculation explained above performed on Prodan molecule in bulk solvents of various polarity agrees with the experimental measurements of the Stokes shift. The dynamics of the coupled solvent relaxation and evolution of the excited state is in excellent agreement with ultrafast transient absorption spectroscopy performed in the Gundlach lab. ☐ The MD/GW-BSE calculation is repeated in a more complex system consisting of Laurdan in DOPC and 1:1 mixture of DOPC/CHOL bilayer. The result of Laurdan simulation does not agree with experimental measurement but provides valuable insights regarding the need to improve Laurdan Force Field parameters. In particular, the results suggest that the MD model for Laurdan is not partitioning correctly at the lipid/water interface. ☐ In order to assess the partitioning of the Laurdan chromophore at the oil/water interface, Adaptive Biasing Force (ABF) Free energy calculation was performed on Prodan in the water-hexadecane slab system. The free energy profile (PMF) of Prodan in the direction perpendicular to the water hexadecane interface was analyzed to obtain the preferred location of Prodan in the water-hexadecane slab, and to determine the bulk partitioning of the Prodan model between water and hexadecane.
Description
Keywords
Fluorescence, GW-BSE, Laurdan, Lipid Bilayer, MD Simulation