Theory of Single-molecule Chemical Dynamics

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Dmitrii E. Makarov of the University of Texas at Austin is supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry. Biomolecules and their assemblies act as machines, performing myriads of tasks in living organisms. These tasks include the synthesis of other molecules, the transport of cargo across cells, generation of mechanical forces, recognition, signaling and others. An understanding of the microscopic chemical basis of these functions will enable the design of bioinspired materials and nanomachines. Such understanding provides important insights into the molecular origins of diseases. A key challenge to achieving this goal is that many molecular motions, e.g. the “power stroke” of a molecular motor, are both too fast to observe via direct experiments and too slow to model on a computer. The Makarov research group uses theory to bridge the gap between experimental observations in single molecule studies and computer simulations of biomolecules in action. Through synergy between experiments, theory, and molecular simulations, they are developing accurate models and theories to describe the motion of biomolecules as inferred directly from experimental observations. This project will increase integration of education and research through organization of a Summer School on molecular kinetics, organization of the Biophysics Day at UT Austin, involvement of undergraduate students in the PI's group research activities, and participation of students in scientific meetings. Outreach efforts will include talks at Texas universities serving underrepresented groups, with the goal to establish relationships with students and faculty, and mentoring a competitive Science Olympiad team of middle and high school students. The studies of the recently discovered novel mechanism of biomolecular interactions may have important implications in the biotechnology, as well as for the development of bioinspired materials with high toughness.The research supported by this grant includes two major components. In the first component, a coherent picture of microscopic biomolecular dynamics at multiple timescales and at different levels (from atomistic to coarse, low-dimensional) of theoretical description is being developed, with the focus on the intrachain dynamics of intrinsically disordered proteins, biomolecular folding, and protein association, especially the formation of “fuzzy” protein complexes. The second component focuses on the dynamics of barrier crossing in nonequilibrium processes such as those underlying the action of molecular machines, with the goal to uncover underlying dynamics, beyond discrete states and transition rates, from high-temporal-resolution single-molecule data. The group also seeks to elucidate how molecular machines break the symmetry between the forward and backward motion.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.