Multiscale modeling of liquid interfacial phases in biomolecular environments and nanomaterials

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It is widely recognized that solvation is critical for a broad range of science and technology. In particular, inhomogeneous liquid phases are of paramount importance in a variety of technological applications of chemistry, electrochemistry, biocatalysis, biology, and pharmacology. Representative examples are electrolyte solution in nanoporous carbon, and protein-drug interactions in intracellular confinement. Modeling liquids at interfaces and in nano-confinement has been attempted at different levels of simplification, 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 solvation theoretical models that adequately include molecular structure of solvent in nanoscale confinement of chemical and biomolecular systems 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.***Based on the first principles of statistical mechanics, integral equation theory of liquids provides a firm platform to handle complex chemical and biomolecular systems in solution. In particular, the three-dimensional reference interaction site model with the Kovalenko-Hirata closure relation (3D-RISM-KH molecular theory of solvation) has provided mechanisms insights and properties predictions for a number of systems in solution otherwise amenable to molecular simulation or continuum solvation treatment. 3D-RISM-KH 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, and Molecular Operating Environment (MOE) drug discovery suite.***This project will couple the 3D-RISM-KH and SS-LMBW approaches in an inhomogeneous 3D-RISM-KH molecular theory of liquid interfaces and confined liquids, and will apply it to complex chemical and biomolecular problems, including: (i) drug discovery and transport across biomembranes and the blood-brain barrier for Alzheimer's and ALS therapeutics, (ii) prediction of cellulose nanocrystals (CNC) nanoparticles translocation across biomembranes towards nanotoxicity database, and (iii) nanoparticles in nanoporous carbon material for energy storage devices. The new methodological developments will be added to the existing implementations in the MOE (Canada) and ADF (Netherlands) software packages. Two PhD students will be involved and trained on this project.********