We develop multiscale modeling methodologies based on combinations of the statistical-mechanical 3D-RISM-KH molecular theory of solvation with quantum mechanics, molecular mechanics and molecular dynamics for the solute macromolecule. In these self-consistent field couplings, the 3D-RISM-KH theory provides accurate description of different solvent systems, solvent mixtures, electrolyte solutions, solvent close to phase transitions, accounts for hydrogen bonding, hydrophobicity, and solvent molecules in cavities of the solute macromolecule. To predict the effect of external conditions on geometry, electronic structure, and electronic transitions in solution, we employ the self-consistent field, Kohn-Sham DFT/3D-RISM-KH multiscale method implemented by our group in the Amsterdam Density Functional (ADF) computational chemistry software, as well as the orbital-free embedding (OFE) method we coupled with 3D-RISM-KH for the electron density of a macromolecule in an environment. We employ these methods for the following:
• Petroleum. We predict the intermolecular and molecule-zeolite interactions of petroleum model compounds and their effect on absorption, emission, NMR and IR spectra to understand the role of hydrogen bonding and π-π interactions in heavy oil aggregation.
• Nanocrystalline cellulose (NCC). An important challenge in NCC research is to accurately predict the degree and type of surface modifications necessary to achieve dispersion without altering crystallinity and mechanical properties. We study the effect of grafting modifications on hydrogen bonding, solvation structure and thermodynamics of NCC, and model the process of cellulose swelling in solution.
• Gelation ability. Theoretical insight into the formation and stability of polymer gels allows establishing a procedure for gelation ability prediction based on calculated mobility and compressibility of a solution.
• Inhibitor docking. We propose a multiscale approach for biomolecular modeling based on the 3D-RISM-KH theory that provides a natural link between different levels of coarse-graining details in the multiscale description of the solvation structure and thermodynamics. This approach is capable of predicting binding sites for the inhibitors of the pathological conversion and aggregation of amyloidogenic proteins in agreement with experimental data.