Sanjib Senapati

Groove Binding Mechanism of Ionic Liquids: A Key Factor in Long-Term Stability of DNA in Hydrated Ionic Liquids?

Nucleic acid sample storage is of paramount importance in biotechnology and forensic sciences. Very recently, hydrated ionic liquids (ILs) have been identified as ideal media for long-term DNA storage. Hence, understanding the binding characteristics and molecular mechanism of interactions of ILs with DNA is of both practical and fundamental interest. Here, we employ molecular dynamics simulations and spectroscopic experiments to unravel the key factors that stabilize DNA in hydrated ILs. Both simulation and experimental results show that DNA maintains the native B-conformation in ILs. Simulation results further suggest that, apart from the electrostatic association of IL cations with the DNA backbone, groove binding of IL cations through hydrophobic and polar interactions contributes significantly to DNA stability. Circular dichroism spectral measurements and fluorescent dye displacement assay confirm the intrusion of IL molecules into the DNA minor groove. Very interestingly, the IL ions were seen to disrupt the water cage around DNA, including the spine of hydration in the minor groove. This partial dehydration by ILs likely prevents the hydrolytic reactions that denature DNA and helps stabilize DNA for the long term. The detailed understanding of IL-DNA interactions provided here could guide the future development of novel ILs, specific for nucleic acid solutes.

Water structure and dynamics in phosphate fluorosurfactant based reverse micelle: A computer simulation study

We performed a molecular dynamics simulation on a system containing a water pool inside the reverse micelle made up of an assembly of phosphate fluorosurfactant molecules dissolved in supercritical carbon dioxide. The water molecules in the first solvation shell of the headgroup lose the water to water tetrahedral hydrogen bonded network but are strongly bonded to the surfactant headgroups. This change in inter-water hydrogen bonding in connection with the confined geometry of the reverse micelle slows down the translational and especially the rotational dynamics of water.

Self-Assembled Inverted Micelles Stabilize Ionic Liquid Domains in Supercritical CO2

Molecular aggregation is a complex phenomenon that is difficult to study in detail experimentally. Here, we elucidate the formation of ionic liquid-in-carbon dioxide (IL-in-CO(2)) microemulsions via a computer simulation technique that demonstrates the entire process of self-aggregation at the atomic level. Our study reveals direct evidence of the existence of stable IL droplets within a continuous CO(2) phase through amphiphilic surfactants. The microstructure of the nanodroplets matches very well with the small-angle neutron scattering data. A detailed investigation of the structural and energetic properties explains why guanidium acetate-based IL-in-CO(2) microemulsions showed a greater stability than imidazolium hexafluorophosphate-based microemulsions in recent spectroscopic experiments. In contrast to the existing hypothesis in literature, the study reveals that the stability of the microemulsions mainly pertains to the IL anion-headgroup interactions, while the cations play a secondary role. The detailed atomic level understanding provides a deeper insight that could help in designing new surfactants for improved IL uptake in CO(2).

Explaining the differential solubility of flue gas components in ionic liquids from first-principle calculations.

Flue gas is greatly responsible for acid rain formation and global warming. New generation ionic liquids (ILs) have potential in controlling the flue gas emissions, as they acquire high absorptivity for the component gases SO(2), CO(2), etc. The association of the IL-gas interactions to the absorptivity of gas molecules in ILs is, however, poorly understood. In this paper, we present a molecular level description of the interactions of ILs with SO(2), CO(2), and N(2) and show its implications to the differential gas solubility. Our results indicate that the IL anion-gas interactions play a key role in deciding the gas solubility in ILs, particularly for polar gases such as SO(2). On the other hand, regular solution assumption applies to N(2) solubility. In accordance with the previous theoretical and experimental findings, our results also imply that the IL anions dominate the interactions with gas molecules while the cations play a secondary role and the underlying fluid structures of the ILs remain unperturbed by the addition of gas molecules.

Molecular dynamics simulations of simple dipolar liquids in spherical cavity: effects of confinement on structural, dielectric, and dynamical properties

The equilibrium and dynamical properties of Stockmayer liquids confined in a spherical cavity are investigated by means of molecular dynamics simulations. The simulations are carried out at varying density and cavity size. Various equilibrium and time dependent quantities such as the spatial and orientational density profiles, dielectric constants, average energies, pressures, components of translational diffusion tensors parallel and perpendicular to the cavity surface, rotational diffusion coefficients and several time correlation functions are calculated and the effects of confinement on the above properties are discussed. The density profiles are found to be highly inhomogeneous near the cavity wall, and the dielectric constant of the liquids in cavity is found to be significantly smaller than that of the bulk phases. The diffusion along the surface normal and also the dipolar orientational relaxation of solvent molecules in cavity are found to slow down because of confinement. The dynamics of solvati...

Understanding the basis of drug resistance of the mutants of αβ-tubulin dimer via molecular dynamics simulations.

The vital role of tubulin dimer in cell division makes it an attractive drug target. Drugs that target tubulin showed significant clinical success in treating various cancers. However, the efficacy of these drugs is attenuated by the emergence of tubulin mutants that are unsusceptible to several classes of tubulin binding drugs. The molecular basis of drug resistance of the tubulin mutants is yet to be unraveled. Here, we employ molecular dynamics simulations, protein-ligand docking, and MMPB(GB)SA analyses to examine the binding of anticancer drugs, taxol and epothilone to the reported point mutants of tubulin - T274I, R282Q, and Q292E. Results suggest that the mutations significantly alter the tubulin structure and dynamics, thereby weaken the interactions and binding of the drugs, primarily by modifying the M loop conformation and enlarging the pocket volume. Interestingly, these mutations also affect the tubulin distal sites that are associated with microtubule building processes.

Self-Assembled Reverse Micelles in Supercritical CO2 Entrap Protein in Native State

Molecular dynamics simulations of random quaternary mixtures of protein-water-CO2-fluorosurfactants show the self-assembly of reverse micelles in supercritical carbon dioxide where the protein becomes entrapped inside the aqueous pool. Analyses show that the protein native state remains intact in the water pool. This is because of the bulk nature of the enclosed water that provides a suitable environment for the extracted protein. Results from ab initio calculations imply that the existing fluorosurfactants can be made more effective in stabilizing water-in-CO2 microemulsions by a partial hydrogenation in their tails. A Lewis acid-Lewis base interaction among CO2 and the surfactant tails enhances the stability of the aqueous droplets substantially. The study can help accelerate the search for surfactant process for environmentally benign applications in dense CO2.

A molecular dynamics simulation study of the dimethyl sulfoxide liquid–vapor interface

In this study, a fully flexible, nonpolarizable model potential of dimethyl sulfoxide (DMSO) has been used to investigate the DMSO liquid–vapor interface, based on classical molecular dynamics simulation techniques. A series of four simulations in the temperature range of 298–373 K is carried out to examine the temperature dependence of the structural, thermodynamic, and dynamical properties. The full Ewald summation technique is employed to account for the long-range electrostatic interactions. Computed bulk properties of the liquid such as density, diffusion are found to be in good agreement with experimental values. Self-diffusion coefficient of bulk DMSO molecules is computed to be smaller than at the interface. The study demonstrates the importance of inclusion of flexibility in the model and the use of Ewald sums, which have an influence on dynamics.

Dynamic flaps in HIV‐1 protease adopt unique ordering at different stages in the catalytic cycle

The flexibility of HIV‐1 protease flaps is known to be essential for the enzymatic activity. Here we attempt to capture a multitude of conformations of the free and substrate‐bound HIV‐1 protease that differ drastically in their flap arrangements. The substrate binding process suggests the opening of active site gate in conjunction with a reversal of flap tip ordering, from the native semiopen state. The reversed‐flap, open‐gated enzyme readily transforms to a closed conformation after proper placement of the substrate into the binding cleft. After substrate processing, the closed state protease which possessed opposite flap ordering relative to the semiopen state, encounters another flap reversal via a second open conformation that facilitates the evolution of native semiopen state of correct flap ordering. The complicated transitional pathway, comprising of many high and low energy states, is explored by combining standard and activated molecular dynamics (MD) simulation techniques. The study not only complements the existing findings from X‐ray, NMR, EPR, and MD studies but also provides a wealth of detailed information that could help the structure‐based drug design process. Proteins 2011;

Nanostructural Reorganization Manifests in Sui-Generis Density Trend of Imidazolium Acetate/Water Binary Mixtures

Ionic liquids (ILs) are emerging as a novel class of solvents in chemical and biochemical research. Their range of applications further expands when a small quantity of water is added. Thus, the past decade has seen extensive research on IL/water binary mixtures. While the thermophysical properties of most of these mixtures exhibited the expected trend, few others have shown deviations from the general course. One such example is the increase in density of the 1-alkyl-3-methyl imidazolium acetate ([Rn mim][Ac])-based ILs with the addition of low to moderate concentrations of water. Although such a unique trend was observed for imidazolium cations of different tail lengths and also from independent experiments, the molecular basis of this unique behavior remains unknown. In this study, we examine the nanostructural reordering in [Rn mim][Ac] (n = 2-6) ILs due to added water by means of molecular dynamics simulations, and correlate the observed changes to the sui-generis density trend. Results suggest that the initial rise in density in these ILs mainly pertains to the water-induced increased spatial correlation among the polar components, where high basicity of the acetate anion plays a key role. At moderate water concentration, the density can rise further for ILs with longer cation tails due to hydrophobic clustering. Thus, while [emim][Ac]/water mixtures exhibit the density turnover at Xw = 0.5, [bmim][Ac] and [hmim][Ac] show the turnover at Xw = 0.7. The detailed understanding provided here could help the preparation of optimal IL/water binary mixtures for various biochemical applications.