Transport Coefficients, Electroelasticity, and Conductivity of Proteins

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Dmitry Matyushov of Arizona State University is supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry to develop theoretical models of Mobility, Electroelasticity, and Conductivity of proteins. Electrons move through proteins in biological respiratory energy chains and in bacterial photosynthesis to store energy for biological function. Speeding up this charge transport is critical for biological performance and efficiency. How proteins achieve sufficiently fast electron transport is still puzzling. Matyushov and his research group will perform high performance computer simulations and modeling to develop understanding of high efficiency of charge transport in proteins. A new and surprising development in this field is the realization that proteins are also high-efficiency conductors, despite long-held view of these materials as insulators. This property provides biological protection from oxidative damage, but also opens the door to new technologies of single-molecule monitoring of biological activity through changes in protein conductivity. Matyushov with experimental colleagues will pursue theoretical modeling of mechanisms of protein conductivity in single-molecule junctions. He will also develop models of separation of proteins from solutions by means of dielectrophoresis. A new theory recently developed in his group predicts high sensitivity of proteins in solution to electric field gradients, which offers new technologies for protein separation in pharmaceutical and biomedical applications. The results of this work will be available to the community in the form of predictive computational algorithms to calculate conductivity of proteins and their sensitivity to the electric field in microfluidic devices. Theoretical results will be disseminated through books and review articles targeting broad audience of engineers and biochemists. The proposed work is to develop formal theories and computational algorithms to address the general problem of nonequilibrium (nonergodic) sampling in proteins and to establish direct links to laboratory experiments. The following research goals will be pursued: (1) Analytical theories of nonergodic sampling and violation of fluctuation-dissipation relations in proteins will address the problem of vectorial charge transport from a slow to a fast medium and the effect of charge fluctuations in proteins on protein redox reactions. (2) Theories of protein translational and rotational diffusivity will be developed in terms of competing forces producing stochastic translations and rotations. Our current effort to develop models of protein dielectrophoresis will be extended to establish practical approaches to capture proteins at nanopores. (3) The development of a theory of single-molecule conductivity of proteins based on the idea of nonergodic sampling of the configuration space by intraprotein charge carriers. (4) A theory of protein viscoelectroelasticity will be developed in terms of frequency-dependent viscoelastic moduli and solvation of ionizable surface residues. The theory will provide memory functions to describe complex dynamics of protein diffusivity and to build a general framework for addressing nonequilibrium fluctuations of forces responsible for protein mobility. Strong connection of the proposed activities to experiment will help graduate students and postdoctoral fellows to gain a broader view of the discipline and learn the culture of collaborative research.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.