Multiscale modeling of compounds and nanoparticles at liquid and soft matter interfaces

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It is widely recognized that solvation is critical for a broad range of science and technology. In particular, liquid interfaces are of paramount importance in a variety of technological applications of chemistry, electrochemistry, biocatalysis, biology, and pharmacology. At liquid interfaces, aqueous and organic solvents meet and create an environment with unique properties that can be fine-tuned to promote reactivity and self-assembly. Soft matter nanostructures are complex liquid interfaces formed by competing chemical functionalities. An important example is a lipid bilayer of biomembranes in living cell and intracellular structures. Modeling structure and functions of liquid interfaces poses a challenge, which has been attempted at separate levels of complexity, from drug transport across a biomembrane estimated as partitioning between bulk liquid phases of water and octanol, to coarse-grained simulations of nanoparticle translocation across a lipid bilayer. At present, there is a need of theoretical models of solvation that adequately include molecular structure of solvent, in particular, in local confinement of chemical and biomolecular nanosystems and nanomaterials. Such theoretical models are of great demand to extend the capabilities of molecular simulations which are by far not sufficient to address complex phenomena and processes on the whole spectrum of scales from fast to very slow in large nanosystems of interest. Theoretical models of solvation based on statistical mechanics can be an essential element coupled to all parts of predictive multiscale modeling including quantum description for chemical structure and active centers, molecular dynamics (MD) and dissipative particle dynamics (DPD) for nanostructures, and coarse-grain models for system functions. Integral equation theory of liquids based on the first principles of statistical mechanics is becoming increasingly popular, as it provides a firm platform to handle complex chemical and biomolecular systems in solution. In particular, the 3D-RISM-KH molecular theory of solvation (three-dimensional reference interaction site model with the Kovalenko-Hirata closure relation) has shown substantial success for a number of systems in solution that otherwise were not amenable to molecular simulation or continuum solvation treatment. It has been advanced to the state of practical applicability and coupled in multiscale methodology with quantum chemistry, MD and DPD simulation methods, and ligand docking protocols, the developments implemented in major software packages: Amsterdam Density Functional (ADF) computational chemistry package, Amber MD package, AutoDock suite of docking tools [9], and Molecular Operating Environment (MOE) package. Furthermore, the site-site generalization of the Lovett-Mou-Buff-Wertheim (SS-LMBW) integro-differential equation constitutes a molecular theory of liquid interfaces which has been validated on planar interfaces of non-polar and complex associating liquids. This project will couple the 3D-RISM-KH and SS-LMBW approaches in a new accurate molecular theory of liquid nd soft matter interfaces, and will apply it to complex chemical and biomolecular problems, including: (i) chemical reactivity of functionalized nanoparticles at liquid interfaces, (ii) drug transport across biomembranes and the blood-brain barrier, and (iii) prediction of translocation of nanoparticles across biomembranes towards nanotoxicity database for nanoparticles of different size and shape, and surface functionalization. The new methodological developments will be added to the existing implementations in the MOE (Canada) and ADF (Netherlands) software packages. Three PhD students will be involved and trained in this project.