Activated and nonlinear kinetics in biomolecules and interfaces

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Dimitry Matyushov of Arizona State University is supported by an award from the Chemical Theory, Models and Computational Methods Program in the Division of Chemistry for theoretical and computational studies of proteins. Proteins provide the main building material of cells and multicellular organisms. In addition, protein enzymes are working horses of the cell catalyzing all chemical reactions required for life. All energy of life is produced and stored by moving electrons in protons across the cellular membrane, a function performed by membrane-bound proteins. At the same time, 80% of the cell's volume is water, which mostly exists in its interfacial form surrounding proteins and lipids of membranes. How proteins and interfacial water, the "matrix of life", couple in their function is still largely a mystery requiring both theoretical and experimental studies. The set of questions, addressed by this project, touches on the deepest problems of energy efficiency of life, its physiological energy flow, and the fundamental principles of work produced by non-equilibrium molecular systems. Professor Matyushov and his research group are actively engaged in an outreach, research and education program involving local high school students. This theoretical project, which is deeply connected to experimental studies, suggests that proteins are fundamentally non-equilibrium systems in which the time-scales of protein function are often shorter than the time-scales of equilibration achieved through conformational dynamics. This non-equilibrium nature of proteins requires two temperatures: the configurational temperature of the non-equilibrium protein and the standard thermodynamic temperature of the surrounding bath. Computational studies performed in the previous funding cycle have shown that proteins are up to three times "hotter"than water. A direct consequence of this perspective is a strong depression of the reaction activation barrier. The catalytic action of the enzyme is very much a function of its non-equilibrium state, which ages to the ?dead state? of the Gibbs distribution due to conformational dynamics exploring the configuration space. The aging process has to be terminated and the enzyme reset before this equilibrium state is reached. The project connects enzymatic efficiency of redox active proteins with the protein-water interfacial structure and glassy aging dynamics of collective variables linked to the activated barrier crossing. The project addresses the following practical questions: (a) Configurational temperature of redox proteins and the dynamics of equilibration with the thermal bath. (b) Theories and simulations of interfacial susceptibility of water and its distinction from water in the bulk. This problem connects to a number of experimental techniques such as depolarized light scattering, THz absorption, dielectric spectroscopy, and protein dielectrophoresis. (c) A theory of non-linear dielectric response of solutions applied to testing of interfaces. Collaborative initiatives as a part of the project aim at linking theory to experiment.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.