University of Alberta,
Keywords: neurodegenerative diseases, Alzheimer's, amyotrophic lateral sclerosis, prion disease, drug design, quantum chemistry, molecular solvation theory, molecular dynamics, dissipative particle dynamics, quasidynamics
Summary:Molecular theory of solvation for nanostructures in both aqueous and non-aqueous solution, a.k.a. Three-Dimensional Reference Interaction Site Model (3D-RISM) with Kovalenko-Hirata (KH) closure relation has been systematically developed and applied to a variety of compounds and biomolecules in a number of solvents, mixtures, electrolyte and non-electrolyte solutions. Based on the first principles of statistical mechanics, 3D-RISM-KH predicts solvation structure and thermodynamics of nanochemical and biomolecular systems, including analytical asymptotics. It yields high accuracy, efficiency, and applicability by multiscale coupling at different space and time scales to get fundamental understanding and prediction for nanomaterials and biomolecules. This method was coupled with Quantum Chemistry, Molecular Dynamics, and Dissipative Particle Dynamics, including examples of helical rosette nanotubes with tunable stability and hierarchy, water promoted supramolecular chirality inversion, formation and stability of self-assembling supramolecular structures of organic rosette nanotubes with ordered shells of inner and outer water, and accurate and efficient dissipative particle dynamics of polymer chains with coarse-grained effective pair potential obtained from DRISM-KH theory. 3D-RISM-KH molecular solvation was also coupled with Multi-Time-Step Molecular Dynamics and Generalized Solvation Force Extrapolation (MTS-MD/3D-RISM-KH/GSFE), providing quasidynamics description of biomolecules. Validation included folding of miniprotein in solution from fully extended to equilibrated state in 60 ns, which yielded acceleration by two orders of magnitude time scale as compared to 4-9 µs protein folding in experiment. Recent developments and applications of 3D-RISM-KH consisted in multiscale coupling of Quantum Chemistry, Molecular Solvation Theory, Molecular Dynamics, Dissipative Particle Dynamics, and Quantitative Structure-Activity Relationship (QSAR) applications. This Multiscale Methods Framework yields dramatically improved accuracy, efficiency, and applicability by coupling models and methods on different scales and providing fundamental understanding and predictions. References:  Kovalenko, A.; Hirata, F. J.Chem.Phys., 1999, 110, 10095; 2000, 112, 10391; 2000, 112, 10403.  Kovalenko, A. In: Molecular Theory of Solvation. Hirata, F. (Ed.) Series: Understanding Chemical Reactivity, Kluwer, Dordrecht, 2003, Vol. 24, pp.169–275.  Kovalenko, A. Pure Appl.Chem., 2013, 85, 159.  Kovalenko, A. Multiscale Modeling of Solvation. In: Springer Handbook of Electrochemical Energy, pp. 95-139. Breitkopf, C.; Swider-Lyons, K. (Eds.) Springer-Verlag Berlin Heidelberg, 2017, 1016p.  Gusarov, S.; Ziegler, T.; Kovalenko, A. J.Phys.Chem.A, 2006, 110, 6083.  Casanova, D.; Gusarov, S.; Kovalenko, A.; Ziegler, T. J.Chem.Theory Comput., 2007, 3, 458.  Kaminski, J.W.; Gusarov, S.; Wesolowski, T.A.; Kovalenko, A. J.Phys.Chem.A, 2010, 114, 6082.  Malvaldi, M.; Bruzzone, S.; Chiappe, C.; Gusarov, S.; Kovalenko, A. J.Phys.Chem.B, 2009, 113, 3536.  Moralez, J.; Raez, J.; Yamazaki, T.; Motkuri, R. K.; Kovalenko, A.; Fenniri, H. J.Am.Chem.Soc., 2005, 127, 8307.  Johnson, R.S.; Yamazaki, T.; Kovalenko, A.; Fenniri, H. J. Am.Chem.Soc., 2007, 129, 5735.  Yamazaki, T.; Fenniri, H.; Kovalenko, A. Chem.Phys.Chem., 2010, 11, 361.  Kobryn, A. E.; Nikolić, D.; Lyubimova, O.; Gusarov, S.; Kovalenko, A. J.Phys.Chem.B, 2014, 118, 12034.  Omelyan, I.; Kovalenko, A. J.Chem.Theory Comput., 2015, 11, 1875.  Hlushak, S.; Kovalenko, A. J.Phys.Chem. C, 2017, 121, 22092.  Kovalenko, A.; Gusarov, S. Phys.Chem.Chem.Phys., 2018, 20, 2947.