Fluorescent Proteins Detect Host Structural Rearrangements via Electrostatic Mechanism
| Autor: | Heiko Lammert, Peter J. Rossky, Lena Simine, José N. Onuchic, Li Sun |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Fluorophore Chemistry Rational design Quantum yield General Chemistry 010402 general chemistry 01 natural sciences Biochemistry Quantum chemistry Fluorescence Catalysis 0104 chemical sciences Green fluorescent protein 03 medical and health sciences Molecular dynamics chemistry.chemical_compound 030104 developmental biology Colloid and Surface Chemistry Biophysics Biosensor |
| Zdroj: | Journal of the American Chemical Society. 140:1203-1206 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | The rational design of genetically encoded fluorescent biosensors, which can detect rearrangements of target proteins via interdomain allostery, is hindered by the absence of mechanistic understanding of the underlying photophysics. Here, we focus on the modulation of fluorescence by mechanical perturbation in a popular biological probe: enhanced Green Fluorescent Protein (eGFP). Using a combination of molecular dynamics (MD) simulations and quantum chemistry, and a set of physically motivated assumptions, we construct a map of fluorescence quantum yield as a function of a 2D electric field imposed by the protein environment on the fluorophore. This map is transferable between Tsien's Class 2 GFP's, and it allows one to estimate the shifts in fluorescence intensity due to mechanical perturbations directly from MD simulations. We use it in combination with steered MD simulations to put forward a hypothesis for the mechanism of a genetically encoded voltage probe (ArcLight) whose mechanism is currently under debate. |
| Databáze: | OpenAIRE |
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