Understanding the unfolding mechanism of human telomeric G-quadruplex using steered molecular dynamics simulation

The unfolding pathway of human telomeric G-quadruplex with three G-tetrads in presence of K+ and Na+ ions, separately using steered molecular dynamics (SMD) simulation is reported. The isothermal-isobaric all-atoms classical molecular dynamics simulation results show that three K+ and three Na+ ions are required within the central channel of the G-quadruplex (PDB ID: 143D and 2HY9, respectively) to stabilize the respective overall structure. To obtain the unfolded G-quadruplex which is ~5-6 times of its initial contour length, SMD simulation has been carried out by fixing one end of the G-quadruplex and constraining the other end to move only along the long axis (z-axis). The SMD results suggest that the unfolding of G-quadruplex occurs via G-triplex intermediates independent of the presence of cations (K+, Na+).

A Thiazole Coumarin (TC) turn-on fluorescence probe for AT-base pair detection and multipurpose applications in different biological systems

Sequence-specific recognition of DNA by small turn-on fluorescence probes is a promising tool for bioimaging, bioanalytical and biomedical applications. Here, the authors report a novel cell-permeable and red fluorescent hemicyanine-based Thiazole Coumarin (TC) probe for DNA recognition, nuclear staining and cell cycle analysis. TC exhibited strong fluorescence enhancement in the presence of DNA containing AT-base pairs, but did not fluoresce with GC sequences, single-stranded DNA, RNA and proteins. The fluorescence staining of HeLa S3 and HEK 293 cells by TC followed by DNase and RNase digestion studies depicted the selective staining of DNA in the nucleus over the cytoplasmic region. Fluorescence-Activated Cell Sorting (FACS) analysis by flow cytometry demonstrated the potential application of TC in cell cycle analysis in HEK 293 cells. Metaphase chromosome and malaria parasite DNA imaging studies further confirmed the in vivo diagnostic and therapeutic applications of probe TC. Probe TC may find multiple applications in fluorescence spectroscopy, diagnostics, bioimaging and molecular and cell biology

A one-dimensional energy diffusion approach to multidimensional dynamical processes in the condensed phase

We propose a generalized one-dimensional energy diffusion approach for describing the dynamics of multidimensional dynamical processes in the condensed phase. On the basis of a formalism originally due to Zwanzig, we obtain a one-dimensional kinetic equation for a properly selected relevant dynamical quantity and derive new analytical results for the dynamics of a multidimensional electron-transfer process, nonequilibrium solvation, and diffusive escape from a potential well. The calculated results for electron-transfer reactions in solvent-separated and contact ion pair systems are found to be in good agreement with the experimental results. We are able to explain the rate of the electron-transfer reaction using much smaller and reasonable values of the solvent reorganization energy in contrast to earlier works that had to use a much larger value. The proposed theory is not only conceptually simpler than the conventional approaches but is also free from many of their limitations. More importantly, it provides a single theoretical framework for describing a wide class of dynamical phenomena

A theoretical study of electron transfer in nanoparticle-catalysed redox reactions

Nanoparticle-catalysed electron transfer reactions have been investigated by using an extended version of the theory of electron transfer reactions for the bridge-mediated three-centre process and approximate expressions for various free energy quantities as well as the matrix elements. It is observed that the calculated rates for nanoparticle-catalysed reactions for the reduction of various dyes by standard reducing agents are considerably higher than the rates of direct electron transfer processes and are also found to agree quite well with recently reported experimental results

Understanding the unfolding mechanism of human telomeric G-quadruplex using steered molecular dynamics simulation

907-912The unfolding pathway of human telomeric G-quadruplex with three G-tetrads in presence of K+ and Na+ ions, separately using steered molecular dynamics (SMD) simulation is reported. The isothermal-isobaric all-atoms classical molecular dynamics simulation results show that three K+ and three Na+ ions are required within the central channel of the G-quadruplex (PDB ID: 143D and 2HY9, respectively) to stabilize the respective overall structure. To obtain the unfolded G-quadruplex which is ~5-6 times of its initial contour length, SMD simulation has been carried out by fixing one end of the G-quadruplex and constraining the other end to move only along the long axis (z-axis). The SMD results suggest that the unfolding of G-quadruplex occurs via G-triplex intermediates independent of the presence of cations (K+, Na+)

One-dimensional description of multidimensional electron transfer reactions in condensed phase

We derive a one-dimensional energy diffusion equation for describing the dynamics of multidimensional electron transfer reactions in condensed phase, which is conceptually simpler and computationally more economic than the conventional approaches. We also obtain an analytical expression for the rate of electron transfer reactions for a general one-dimensional effective potential as well as an energy dependent diffusitivity. As an illustrative example, we consider application to electron transfer in a contact ion pair system modeled through harmonic potentials consisting of two slow classical modes and a high frequency vibrational mode for which the numerical results calculated using the proposed one-dimensional approach are shown to be in good agreement with experimental results. The energy diffusion equation and the rate expression for electron transfer obtained from the present theory, therefore, open up the possibility of describing the dynamics of electron transfer in complex systems, through a simpler approach