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Artëm E. Masunov
Computational Molecular and Nanomaterials, Theoretical Chemistry and Molecular Physics
Chemistry of Quantum Dots |
Research
Theoretical and experimental study on H-bonded aggregation: toward rational control over amyloid fibril formation.
Amyloid fibril is a form of protein self-assembly of 8-13 nm in diameter and several μm in length, where ß-strands are arranged perpendicular to the axis of the fibril, and ß-sheets ran parallel to it. In vivo their formation had been associated with spider silk and several "diseases of protein misfolding": Alzheimer's and Parkinson's diseases, where protein looses its native a-helical structure and aggregates. In this project we use molecular simulations to describe non-additive hydrogen bonding in aqueous solution, and build detailed kinetic model with reliable protein-specific parameters for each step of the mechanism. Based on this model, we design small molecules which are able to terminate fibril growth and slow down the progress of the disease.
Figure: Quantum Chemistry of Quantum Dots: HOMO calculated at DFT level (B3PW91/ LANL2mb) in Cd_32Se_14(SeH)_36(PH_3)_4, the cluster modeling colloidal quantum dot of 2 nm in diameter. Electronic structure of quantum dots strongly depends on passivating ligands.
Biomedical use of two-photon absorption: computer-assisted design of non-linear optical materials for photodynamic therapy and fluorescent labels.
Two-photon (TP) fluorescent microscopy employs nonlinear optical process when molecule simultaneously absorbs two photons and emits one. It has a number of advantages over the standard (linear) microscopy, including high three-dimensional resolution (due to quadratic dependence on intensity), and increased penetration depth in tissue with reduced photodamage (by operating with incident light in the visible red-NIR region). These allow for real-time imaging of the living tissue, if effective TP absorbing chromophores are introduced into it. In this project we apply virtual screening and combinatorial chemistry methods to design better TP chromophores. Recently we developed a novel approach to prediction of non-linear optical properties, based on Time-Dependent Density Functional Theory. It gives accurate TP cross-sections for large conjugated molecules. We are improving the accuracy of this method further by taking into account vibrational line broadening, and selecting significant molecular descriptors for nonlinear optical properties. Based on these descriptors, new molecules will be designed from molecular fragments collected in a virtual library and suggested as candidates for an experimental study.
Among the findings of my past research projects are: first topological analysis of experimental electron density in crystal, local models of superconductivity in cuprates, understanding the role of secondary bonds in structures of inorganic dihalides and molecular crystals, ab initio prediction of polymorph relative stability, first comprehensive molecular dynamics study of potential of mean force between ionizable aminoacid sidechains in aqueous solution, development of intermediate (between micro- and macroscopic) solvation model, extension of Density Functional Theory to strongly correlated systems, and discovery of counterion-induced charge transfer excited states of organic chromophores in aqueous solution.
Select Publications
- Masunov A., Tretiak, S. Prediction of two photon absorption properties of organic chromophores using the time-dependent density functional theory. J. Phys. Chem. B 108(3): 899-907, 2004
- Masunov A. When density functional theory goes wrong and how to fix it: spin balanced unrestricted Kohn-Sham formalism. arXiv.org/abs/physics/0310106, 2003
- Masunov A, Lazaridis T. Potentials of mean force between ionizable amino acid side chains in water. J. Am. Chem. Soc. 125(7): 1722-30, 2003
- Dannenberg JJ. Haskamp L. Masunov A. Are hydrogen bonds covalent or electrostatic? A molecular orbital comparison of molecules in electric fields and H-bonding environments. J. Phys. Chem. 103(35): 7083-7086, 1999
- Vyboishchikov S.F., Masunov A.E., Streltsov V.A., Zorkii P.M., Tsirelson V.G. Topological analysis of electron density in a chlorine crystals. Russ. J. Phys. Chem. 68(11): 1837-1840, 1994
- Masunov A.E., Gladkikh O.P., Zorkii P.M. Structure-relaxation mechanism of electrical conductivity of crystals. Russ. J. Phys. Chem. 67(7): 1275-1277, 1993
- Masunov A.E. Stereoelectronic model of the structure of layered crystals of binary dihalides. Russ. J. Coord. Chem. 19(4): 242-249, 1993
- Zorky P.M., Masunov A.E. X-ray diffraction studies on electron density in organic crystals. Russian Chemical Reviews. 59(7):529-606, 1990
Graduate Students
Students will have opportunities to apply their knowledge and widen their horizons in interdisciplinary filed of Nanoscience, including Biochemistry and Materials Science, Biology and Physics, Computers and Device Engineering. They will learn a wide variety of Computational Chemistry techniques including methodological developments, applications, or both. Students will have a choice of different projects, such as computer-assisted design of nonlinear optical materials (for bioimaging and photodynamic therapy), catalytic effects of ceria nanoparticles (to slow down biological aging), control over growth of carbon nanotubes (for microelectronics applications) and amyloid fibrils (Parkinson's disease treatment), development of polarizable force fields to describe clathrates (hydrogen storage materials) and protein/lignad interactions (computational drug design), methodological developments of density functional theory (for description of strongly correlated systems) and implicit solvation models (for more accurate simulations of soft condensed matter). The acquired experience and problem-solving skills will open the doors to successful careers in industry and academia.
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