Theoretical studies of chemical dynamics in complex systems: Nanoconfined water, microdroplets, biomolecular hydration layer, and water-mediated protein association
The thesis contains theoretical studies of the structure and dynamics in different complex systems. Depending on the systems and properties of interest we divide the thesis into five parts. In the first part, we study chemical dynamics in nanoconfined water. Here we primarily focus on the dielectric properties of dipolar fluids confined inside nano-containers of various sizes and shapes. We discover an extremely slow convergence of the static dielectric constant (ε) of water with the size of the nanospheres. Our studies reveal an ultrafast relaxation of the collective orientation of water which is absent in the Stockmayer fluid. We connect this anomaly to the substantially low value of the Kirkwood g-factor for spherically confined water. We extrapolate the values of ε to obtain its true value in the thermodynamic limit which corroborates well with the values in periodic systems. We perform molecular dynamics simulations with three different liquid-surface interactions to study the surface effects. The dielectric response of water under becomes anisotropic in non-spherical confinements, namely, cylindrical and slab geometries. Because of the difference in the dielectric boundary conditions along the different directions, the eigenvalues of the dielectric tensor becomes unequal. We derive the fluctuation formulae for the anisotropic dielectric constants. For the cylindrical geometry, we find that the axial component (εz) and the perpendicular component (εx/y) converge to the bulk value, with the diameter of the nanotube, in an opposite manner. εx/y shows relatively slower convergence starting from a lower value whereas εz shows faster convergence starting from a higher value. For the slab system, the parallel component (ε∥) does not show much deviation from the bulk value. On the contrary, the perpendicular component (ε⊥) exhibits extremely low values for smaller systems and shows a slow convergence toward bulk. Interestingly, in the slab geometry, the dielectric relaxation along the perpendicular direction becomes ultrafast with pronounced oscillations. Our results match well with recent dielectric microscopy experiments. We perform a constrained Ising model-based analysis and to understand the inwardly propagating destructions among correlations. In addition to the above, we study the heterogeneous dynamics of water inside nano-enclosures of different shapes. We investigate the position-dependent solvation of model ionic/dipolar probes and find that the slow components of solvation show highly non-monotonic behaviour with the distance of the probe from the surface. To study the static and dynamical heterogeneity, we obtain the non-Gaussian parameter [α2(t)] and non-linear density response function [χ4(t)]. α2(t) shows an anomalous long-time growth for non-spherical systems which we attribute to the slow dynamics of water along the non-periodic direction(s). In the second part, we focus on the chemical dynamics in small-sized (~μm) droplets that exhibit noticeably different chemistry than bulk water. Several chemical reactions show markedly enhanced rates in the droplet media. Here we present a generalized theoretical model and analytically solve the adjoint equations for two- and three-dimensional systems. We obtain exact expressions for the mean search time (MST) that is found to be proportional to R2/D [R=radius, D=relative diffusion constant]. We carry out Brownian dynamics simulations and show that the MST of reactive partner search in droplets is orders of magnitude smaller than that in the bulk. As the experiments often use an external electric field to charge the droplets, we study the effect of ions and electric fields on the bond dissociation energy. We find that the presence of an ion or electric field weakens the bond and enhances the intrinsic reaction rate. Our results describe the interplay between diffusion control and activation controlled processes. In the third part, we study the dynamics of interfacial water molecules in the biomolecular hydration layers. Here we first aim to resolve a long-standing controversy regarding the timescale of water dynamics in the protein hydration layer, that is, solvation dynamics and dielectric relaxation finds substantial slow relaxation whereas NMR experiments find retardation only by a factor of 2-3. To this goal, we obtain distributions of single-particle relaxation timescales and show that the average values obtained from experiments hide the true picture. To our surprise, we find the existence of both faster and slower than bulk water molecules in the hydration layer. We unravel the origin of disparate timescales (from sub-100 fs to hundreds of ps) observed in the solvation dynamics of natural probe tryptophan tagged to three different proteins- Lysozyme, Myoglobin, and sweet protein Monellin. We show that the neighbourhood charged residues and the intrinsic side-chain fluctuations contribute to the observed slow dynamics. We further decompose the response into protein core, side-chains, and water contributions to study the nature of coupling. We find surprising anti-correlation between the energy fluctuations of protein and water. Our simulation results support the widely discussed protein-solvent slaving picture developed from earlier Mössbauer spectroscopy experiments. We also study the origin of the power law decay observed in DNA solvation dynamics. We employ the Oosawa model, continuum model, mode coupling theory, and continuous time random walk based analyses to unearth the effect of counterion motions. We study the solvation dynamics of DNA bases and a minor groove bound probe. In the fourth part, we characterize the various protonated forms of metformin hydrochloride (MET) by employing computational and spectroscopic techniques. We develop an AMBER based force-field for three protonation states of MET and validate them against available experimental results. We use this force-field to study the interaction of MET with double-stranded B-DNAs. As there is evidence of anti-tumour and anti-cancer activity of MET, we aim to understand its mode of binding with DNA. We employ metadynamics based advanced sampling techniques to obtain the free energy landscape of the binding process. We find that MET prefers AT-rich minor grooves through non-intercalative mode of binding. We confirm these claims from fluorescence spectroscopy and circular dichroism experiments. In the fifth and last part of the thesis, we study the structure and aggregation of insulin oligomers (dimer and hexamer) in water and water-ethanol binary mixtures. Insulin is biologically active in its monomeric form but gets stored in the pancreas as hexamers. The inter-conversion between monomer and hexamer occurs via dimeric intermediates. Here we present the structural analysis of insulin hexamer in water and water-ethanol binary mixture by using atomistic molecular dynamics and X-ray crystallography. We find that the water molecules trapped inside the central hydrophilic cavity of hexamer play a central role in sustaining the robust barrel-shaped structure. The presence of ethanol (even in lower concentrations) deforms the hexameric assembly. Next, we study the energetics of the insulin dimer association/dissociation process. We obtain the free energy landscape from parallel tempering metadynamics simulations in a well-tempered ensemble with respect to two collective variables- inter-monomeric distance and the number of inter-monomeric contacts. We find that the activation barrier of dissociation drastically decreases in the presence of 5% and 10% (v/v) ethanol. We attribute this effect to the preferential solvation of the dimer forming hydrophobic surface of the monomers that results in the destruction of inter-monomeric hydrogen bonding. We analyze the evolving structures along the minimum energy pathway and establish the role of the solvent.