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Computational Physical Chemistry and Biochemistry

We study the stability of chemical and biochemical systems by investigating their dynamics using computer modelling. Computer simulations is a powerful tool in exploring microscopic details of physical and chemical phenomena. Sizes of systems that are investigated range from small clusters to systems containing hundreds of thousand atoms. We focus on the development and application of Molecular Dynamics and Monte Carlo techniques to study rare event dynamics. These critical events, that are usually identified with the transition state of the process, are a bottle-neck in the simulations of a variety of systems of chemical and biological interest. The systems are modelled at the atomic scale using different levels of description in order to capture features defining the properties of the systems.

Development of methods for rare event dynamics

Chemical reactions in solution, nucleation procesesses in phase transitions, conformational changes of macromolecules are examples of chemical processes that occur on long time scales. Such time scales cannot be easily accessed using direct Molecular Dynamics techniques using presently available computer resources. In order to solve these problems we develop new effective methods of the configurational space sampling.
Regions of the phase diagram in the system of $\xi = \lambda/L$ and $L/R$ coordinates. Contiguous lines correspond to constant values of the interaction parameter $B_{\mathrm{ex}}$. The gray region in all subplots indicates location of the restricted domain (see details in the text). The plot shows an overall view of the minima of the droplet energy. Representative snapshots of simulations of charged PEG in water droplets that correspond to the various regions of the phase diagram are also shown.
Using chemical insight and results of direct computer modelling we investigate a reaction coordinate (or a set of such coordinates) that is pertinent to the physical process. The phenomena that are studied are complex and the degrees of freedom of the environment, for example the solvent, has to be taken into account when choosing the reaction coordinate. Reversible work profiles and sampling of trajectories initiated at the transition state reveal the reaction mechanism and allows for the computation of the rate. We have indentified new problems for the application of methods of activated processes, such as the fragmentation of charged droplets at a low ratio of the square of the charge to volume of the droplet; extrusion of macromolecules from droplets. In these systems we have developed new reaction coordinates. We apply advanced sampling techniques such as Multiple Replica Repulsion and transition path sampling to calculate free energy profiles and associated equilibrium constants for non-covalently bound complexes involving nucleic acids, proteins and other macromolecules.

Stability of charged droplets with applications in electrospray ionization

My research group uses molecular simulations and analytical methods combined with analysis of experimental data as principal techniques to study the various facets of the vast world that is cluster and droplet environment. The droplets in question are composed of solvent and charge carriers that may be simple ions such as sodium, potassium, macromolecular ions (protonated peptides, charged polyethylene glycol) and complexes of macromolecules such as small interfering RNA (si-RNA), dsDNA or complexes of proteins. Highly charged droplets present atypical chemical environment with distinct properties characterized by high ionic concentrations. The questions that we pose are on the interactions of ions with macromolecules, stability of complexes of macrolecules and creation of assembled structures in the droplet environment. The questions are intimately connected to the concomitant topics of solvation of neutral and charged macromolecules in clusters and droplets; chemical reactions between charge carriers and macromolecules; release of macromolecular ions from droplets; evaporation of droplets; role of acidity in the charge states of proteins; clustering/declustering of peptides in droplets. In order to understand the factors that differentiate the behaviour of the macromolecules in the droplet environment vs. the bulk solution, we also investigate the charge states and conformational changes in the bulk solution. The studies of charged macromolecules in bulk and droplet environments perform central role in such diverse subjects such as poly-electrolytes in solution (e.g. DNA, proteins); and experimental methods such as electrospray ionization (ESI) and ion-mobility spectroscopy (IMS) where jets of charged nanodroplets with macromolecules is a critical intermediate state. Our computational studies provide the molecular understanding in experiments that use electrospray ionization (ESI). Examples of such experiments are found in the usage of ESI in transfer of analytes from bulk solution into the gas phase for mass spectrometry (MS) analysis, deposition of materials and creation of nanoparticles with controlled morphologies. The outcome of these applications is vast. They lead to the understanding of the interactions among biological molecules, discovery of pharmaceuticals, increased security in transportation by detection of explosives in the airports, efficient chemical analysis, industry production.

Nanopores and confinement

Zeolite molecular sieves are microporous aluminosilicate framework materials containing channels and cavities with molecular dimensions . They are widely used in industry as ion-exchangers, sorbents and catalysts. In the last decade, the increased awareness of the environmental hazards that are caused by chlorinated halocarbons has led to the development of new separation and catalytic conversion processes that utilize zeolites. The effectiveness of zeolites is based on its porous nature and on the distinct interactions between the zeolitic hosts and adsorbed guest species. Among the chemical and physical transformations that a zeolite may induce to a guest molecule, in our research we consider conformational changes of the adsorbed guest molecule due to electrostatic interactions with the zeolite framework. The existence of different conformers of the guest molecule is one of the factors that affects the separation efficiencies of zeolites. Different conformers can have different electric dipole and quadrupole moments, and these molecular properties can affect the heats of adsorption and diffusion of the guest molecules inside the zeolite hosts. In the figures conformations of 1,1,2-trichloro ethane (TCE) in Faujasite (FAU) structure zeolites including sodium Y (Na-Y) and siliceous Y (Si-Y) are shown.

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