Dispersion Correction Alleviates Dye Stacking of Single-Stranded DNA and RNA in Simulations of Single-Molecule Fluorescence Experiments
| Autor: | Mark F. Nueesch, Marcel Heinz, Kara K. Grotz, Lukas S. Stelzl, Gerhard Hummer, Benjamin Schuler, Erik D. Holmstrom |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
010304 chemical physics Stacking Water DNA Molecular Dynamics Simulation Single-molecule experiment 01 natural sciences Fluorescence Surfaces Coatings and Films Nucleobase 03 medical and health sciences Molecular dynamics 030104 developmental biology Förster resonance energy transfer Chemical physics 0103 physical sciences Fluorescence Resonance Energy Transfer Materials Chemistry RNA Physical and Theoretical Chemistry Conformational ensembles Fluorescence anisotropy Fluorescent Dyes |
| Zdroj: | The Journal of Physical Chemistry B. 122:11626-11639 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.8b07537 |
| Popis: | We combine single-molecule Forster resonance energy transfer (single-molecule FRET) experiments with extensive all-atom molecular dynamics (MD) simulations (>100 μs) to characterize the conformational ensembles of single-stranded (ss) DNA and RNA in solution. From MD simulations with explicit dyes attached to single-stranded nucleic acids via flexible linkers, we calculate FRET efficiencies and fluorescence anisotropy decays. We find that dispersion-corrected water models alleviate the problem of overly abundant interactions between fluorescent dyes and the aromatic ring systems of nucleobases. To model dye motions in a computationally efficient and conformationally exhaustive manner, we introduce a dye-conformer library, built from simulations of dinucleotides with covalently attached dye molecules. We use this library to calculate FRET efficiencies for dT19, dA19, and rA19 simulated without explicit labels over a wide range of salt concentrations. For end-labeled homopolymeric pyrimidine ssDNA, MD simul... |
| Databáze: | OpenAIRE |
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