Origin of Slow Solvation Dynamics in DNA: DAPI in Minor Groove of Dickerson-Drew DNA

Abstract

The measurement and understanding of collective solvation dynamics in DNA have vital biological implications, as protein and ligand binding to DNA can be directly controlled by complex electrostatic interactions of anionic DNA and surrounding dipolar water, and ions. Time-resolved fluorescence Stokes shift (TRFSS) experiments revealed anomalously slow solvation dynamics in DNA much beyond 100 ps that follow either power-law or slow multiexponential decay over several nanoseconds. The origin of such dispersed dynamics remains difficult to understand. Here we compare results of TRFSS experiments to molecular dynamics (MD) simulations of well-known 4′,6-diamidino-2-phenylindole (DAPI)/Dickerson-Drew DNA complex over five decades of time from 100 fs to 10 ns to understand the origin of such dispersed dynamics. We show that the solvation time-correlation function (TCF) calculated from 200 ns simulation trajectory (total 800 ns) captures most features of slow dynamics as measured in TRFSS experiments. Decomposition of TCF into individual components unravels that slow dynamics originating from dynamically coupled DNA-water motion, although contribution from coupled water-Na + motion is non-negligible. The analysis of residence time of water molecules around the probe (DAPI) reveals broad distribution from ∼6 ps to ∼3.5 ns: Several (49 nos.) water molecules show residences time greater than 500 ps, of which at least 14 water molecules show residence times of more than 1 ns in the first solvation shell of DAPI. Most of these slow water molecules are found to occupy two hydration sites in the minor groove near DAPI binding site. The residence time of Na + , however, is found to vary within ∼17−120 ps. Remarkably, we find that freezing the DNA fluctuations in simulation eliminates slower dynamics beyond ∼100 ps, where water and Na + dynamics become faster, although strong anticorrelation exists between them. These results indicate that primary origin of slow dynamics lies within the slow fluctuations of DNA parts that couple with nearby slow water and ions to control the dispersed collective solvation dynamics in DNA minor groove.

Cholic-Acid-Derived Amphiphiles Can Prevent and Degrade Fungal Biofilms

“…Antifungal activities, biofilm prevention and degradation assays, Live/Dead staining of planktonic and C. albicans biofilms, scanning electron microscopy, and transmission electron microscopy experiments were performed as per published protocols. 43 Time-Resolved Fluorescence Spectroscopy. For performing time-resolved fluorescence decay measurements, a log-phase culture of C. albicans was taken.…”

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“…On day 7, luciferin substrate (20 μL of 10 mg/mL) was injected at catheter site and bioluminescence imaging was done. 43 Catheters were then removed and vortexed for 20 min in 1 mL of saline coupled with intermittent sonication. Suspensions were plated and colonies obtained after 48 h were counted and represented as log 10 CFU/mL values.…”

Femtosecond Laser Induced Luminescence in Hierarchically Structured Nd3+,Yb3+,Er3+ Co-Doped Upconversion Nanoparticles: Light-Matter Interaction Mechanisms from Experiments and Simulations

“…Thanks to remarkable advances in theory, computation, and experiments, nowadays it is possible to interrogate a variety of molecular and material processes that cover many orders of magnitude in time. Starting from the earliest fundamental events up to longer times, studies performed at multiple timescales include, for example, glasstransition [1,2], biophysics [3,4] and solar cells [5]. That the examples mentioned span multiple fields of research already speaks for the widespread interest in this growing class of interdisciplinary tools.…”

Femtosecond Laser Induced Luminescence in Hierarchically Structured Nd3+,Yb3+,Er3+ Co-Doped Upconversion Nanoparticles: Light-Matter Interaction Mechanisms from Experiments and Simulations

“…Thanks to remarkable advances in theory, computation, and experiments, nowadays it is possible to interrogate a variety of molecular and material processes that cover many orders of magnitude in time. Starting from the earliest fundamental events up to longer times, studies performed at multiple timescales include, for example, glasstransition [1,2], biophysics [3,4] and solar cells [5]. That the examples mentioned span multiple fields of research already speaks for the widespread interest in this growing class of interdisciplinary tools.…”