Dispersed Slow Solvation Dynamics in DNA
DNA is a poly-anionic macromolecule. At physiological condition DNA gets neutralized/stabilized by the positively charged counterions and dipolar water in its vicinity. These ions and water and also the DNA have their characteristic dynamics which defines the overall dynamics of the complex DNA system. The dynamics of water and ions in-and-around DNA play a vital role in the interaction of DNA with proteins and other small molecules/drugs. In fact, any molecular recognition by DNA is associated with rearrangement of water and ions from the vicinity of the molecular binding-site in DNA. In this project, we study the dynamics in duplex and higher order G-quadruplex DNA by applying time-resolved (fluorescence) techniques, so as to understand the dynamics of water and ions near DNA probed by a ligand molecule. Our aim is to understand how the water dynamics gets perturbed near DNA and how they are interrelated. For this we apply extensive atomistic molecular dynamics (MD) simulation in these DNA/ligand systems to understand the origin of the dispersed dynamics, as we find in our experimental studies. Our current endeavour goes into comparing the MD simulation results directly with the experimental results in order to understand the intricate dynamic coupling of water, ions and DNA-proper.
(For example see, JPCB 2019, J. Biosciences 2018, Rev. in Fluorescence 2017, MAF 2016, JPCL 2015, JPCL 2012, JACS 2010, JACS 2009)

Base-Sequence & -Mismatch Dependent DNA Dynamics
Binding of proteins and ligands to DNA occurs in base-sequence dependent manner. Also, various enzymes recognize and repair base-mismatches and other DNA damages through BER or NER pathways. Questions remain that how proteins and ligands can bind specifically to a specific base-sequence and/or recognize base-mismatches? Is there any base-sequence and base-mismatch specific local dynamic signature present within DNA? These questions we try to understand through the probing of signature dynamics of specific base-sequence and base-mismatch within DNA double helix using ultrafast fluorescence Stokes shift experiments in femtoseconds to nanoseconds time-range. Such studies can unravel unique (fastest) dynamical signatures of these DNA base-specific motions which may be important for binding of specific protein and ligand to DNA.
(For example see, JPCB 2017, JPCB 2015)

Slow DNA Dynamics: Effect of Molecular Crowding
The biological functions of nucleic acids occur in crowded cellular environment. Hence, one can ask crucial question that whether the DNA dynamics observed in dilute buffered solution  retains its character within crowded cellular environment, especially in nucleus of cell where the DNA is wrapped around the complex histone protein complex. Such dynamic studies within real biological cell are difficult. Hence, researchers often mimic such crowded environment by adding various background molecules, termed as molecular crowders, in solution which resembles the cell-like environment with lower dielctric constant, higher viscosity, lower water activity, etc. We recently started to explore the dynamics in duplex and higher order G-quadruplex DNA in absence and presence of various synthetic molecular crowders by applying time-resolved fluorescence Stokes shift experiments, together with extensive molecular dynamics (MD) simulation. We are also involved in exploring similar studies inside nucleus of real biological cells.
(For example see, JPCB 2022)

Study of Ligand/DNA Interactions
DNA interacts with various small molecules / drugs so as to form stable complexes and perform several important biochemical processes. Various small molecules/drugs are identified which bind (non-covalently) to DNA grooves or intercalate between base-pairs or pi-stack with DNA bases. Understanding the kinetic pathways of such ligand/DNA interactions are important to develop better small molecules that can target DNA with higher efficiencies. Although bulk spectroscopic techniques can provide information of overall binding constant or free energy of binding of ligands to a biomolecule, it is somewhat difficult to obtain the information about reaction-time as well as the association and dissociation rates of such reaction. Applying fluorescence correlation spectroscopy (FCS) as well as equilibrium and biased metadynamics simulations our group is involved in studying various ligand/DNA interactions at (near) single molecule level to unfold the kinetic pathways of such reactions.
(For example see, Anal. Chem. 2012)

Study of Bio-mimetic Supramolecular Assemblies

The use of bio-mimetic systems such as micelles, reverse micelles (microemulsion droplets), cyclodextrins, etc. are widely explored for studying various fundamental bio-chemical processes that are difficult to study in (real) complex biological systems. Besides, these systems can act as nano-reactors for several chemical processes to occur, such as nano-structures growth. However, characterizing their fundamental properties accurately, such as size-parameters and nano-structure growth kinetics remain extremely difficult. Applying fluorescence correlation spectroscopy (FCS), our group is involved in characterizing the accurate size and size-distributions of such supramolecular systems in solution as well as growth kinetics of nano-structures inside reverse micelles (microemulsion droplets) at (near) single molecule level. Such characterization becomes much more complicated using other available experimental techniques, such as only DLS or TEM.
(For example see, JPCB 2016, JACS 2012, Anal. Chem. 2011)   

Dynamics and Molecular Interactions in Lipid Membrane

Our group is engaged in exploring the static and dynamic properties of lipid/water interfaces using novel fluorescent molecules synthesized by us. We introduced a new family of fluorescent lipid probes which can report on depth-dependent static and dynamics properties across lipid/water interface at sub-nanometer length-scale. We apply steady-state, time-resolved experiments as well as atomistic MD simulation to study and understand various interfacial properties of biological lipid membranes using 4AP-Cn and dansyl based lipid probes. We are also trying to utilize spectroscopic and super resolved fluorescence imaging tools to divulge the position and alkyl chain length dependent solvation properties of real bacterial cell membrane. Our exploration also extends into seeing the effect of various antibiotic molecules on the membrane structures of the E.Coli through fluorescence imaging techniques through collaboration with other research groups.
(For example see, PCCP 2017, PCCP 2016)

Diffusion Dynamics of Membrane Proteins

We, together with our collaborator, explore the application of fluorescence correlation spectroscopy (FCS) in biological (fungal) cell-membrane to study the diffusion dynamics of membrane-bound (Ras) proteins to observe the effect of various mutations and environmental conditions and understand the drug action pathways in fungal cells. These explorations show that it is possible to track the protein dynamics in cell-membranes at single molecule level using FCS.
(For example see, Sci. Rep. 2018)