Sequence-Dependent Solvation Dynamics of Minor-Groove Bound Ligand Inside Duplex-DNA

Abstract

Ligand binding to minor-grooves of DNA depends on DNA-base sequence near its binding-site. However, it is not known how base-sequences affect the local solvation of ligand inside minor-grooves of DNA. Here we present a comprehensive study on sequence-dependent solvation dynamics of ligand inside duplex-DNA by measuring the static and dynamic fluorescence Stokes shifts of a popular groove-binder, DAPI, inside DNA minor-grooves created by four different sequences; d(5'-CGCGAATTCGCG-3')2, d(5'-CGCGTTAACGCG-3')2, d(5'-CGCGCAATTGCGCG-3')2, and d(5'-CGCGCTTAAGCGCG-3')2, having different sequences near DAPI-binding site. Fluorescence up-conversion and time-correlated single photon counting techniques are employed to capture the dynamic Stokes shifts of DAPI over five decades in time from 100 fs to 10 ns. We show that the ligands sense different static and dynamic solvation inside minor-grooves created by different sequences: Only subtle change in the dynamics is seen in DNA containing -AATTG-, -TTAAG-, and -AATTC- sequences, which show power-law relaxation in initial time-decades, followed by biexponential decay in nanosecond time-scales. However, changing a single base (and the complementary base) near ligand-binding site from -TTAAG- to -TTAAC- drastically induces the dynamics to follow a single power-law relaxation over the entire five decades. The observed variation of dynamics possibly relate to the local DNA motions, coupled to the hydration dynamics near the ligand-binding site.

Dispersed dynamics of solvation in G-quadruplex DNA: comparison of dynamic Stokes shifts of probes in parallel and antiparallel quadruplex structures

“…Recently, our group have shown that the dynamic Stokes shift of groove-bound DAPI in duplex DNA follows a similar power law until ~100 ps-although beyond 100 ps the dynamics converge to equilibrium through exponential relaxations [11,12]. It has also been shown that such dynamics are modulated by the change in base sequences near the DAPI binding site [13]. However, it was not known how the dynamics of solvation occur in higher order GqDNA structures until our group reported the first study of the dynamic Stokes shift of groove-bound DAPI in antiparallel hTelo22 GqDNA [19].…”

“…The hydration dynamics around these biomolecules, perturbed by them, facilitate many important biochemical processes such as protein folding [3], enzyme catalysis [4], DNA-protein [5,6] and DNAligand interactions [7,8]. In fact, such hydration dynamics, coupled with biomolecular and counterion motion, can give rise to the dispersed dynamics of solvation in DNA and proteins [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, this effect is found to be significant in DNA [9][10][11][12][13][14][15][16][17][18][19], possibly because of the complex coupled motions of charged DNA, water and ions, which on most occasions show dispersed solvation dynamics from femtoseconds to nanoseconds, inherently following a power law relaxation [9][10][11][12][13][14][15][16].…”

Fluorescence Dynamics in the Endoplasmic Reticulum of a Live Cell: Time‐Resolved Confocal Microscopy

“…The Fee‐Maroncelli protocol requires recording the absorption spectrum of the ER‐Tracker dye, which is almost impossible under a few molecules condition in a live cell. Recently, Sen and co‐workers suggested that ν (0) and hence the missing component of solvation may be obtained from recording absorption spectra of the solvation probe in a rigid matrix at low temperature . However, this method is also not applicable in our case, because it is doubtful whether the micro‐environment of the ER region would be the same when a live cell is frozen.…”

Solvatochromic fluorene-linked nucleoside and DNA as color-changing fluorescent probes for sensing interactions

“…Previous investigations of DNA solvation dynamics were performed with probes placed inside the duplex-DNA either by covalent attachment or by non-covalent minor groove binding. 36 The characterized dynamics in DNA were found to be nonexponential and extended into subpicosecond to nanoseconds timescales, best described by a power-law relaxation. 37 There is no unified explanation of such dispersed dynamics primarily because of the complicated coupling between motions of components localized in the closest (<1 nm) vicinity of the probe: water molecules, segments of the DNA molecule as well as cations.…”

“… 37 , 40 However, in all these cases, except for HNF, a minor, but significant nanosecond component is present. 36 , 41 …”