Transport coefficients, electroelasticity, and conductivity of proteins

Project: Research project

Project Details


Transport coefficients, electroelasticity, and conductivity of proteins Transport coefficients, electroelasticity, and conductivity of proteins Overview: Proteins participate in transfer of charge over long distances in biological energy chains. Low barriers for these processes become possible due to the violation of the fluctuation-dissipation theorem (FDT) by the protein-water statistical ensemble. Recent experimental findings of significant singlemolecule conductance of proteins point to a similar mechanism, despite the accepted view that proteins are insulators. The mechanism of FDT violation involves highly dispersive dynamics of the electric field inside the protein, which are retarded by four orders of magnitude compared to the bulk. Such slow dynamics, and nonergodicity caused by it, make activation barriers for functional charge transfer and hopping conductivity dramatically reduced. While nonergodicity is realized as an important factor in proteins catalytic functions, there are currently no theories capable to bridge between the limits of nonergodic dynamic freezing and full Gibbsian sampling to qualitatively describe nonequilibrium and equilibrium limits of activated dynamics. Similar effects of complex dynamics of the protein and its hydration shell are involved in protein diffusivity where van der Waals and electrostatic forces compete and compensate each other in random kicks producing translational and rotational diffusion. Standard linear theories of dielectric friction are grossly inadequate for protein diffusion and a new paradigm is required. The balance between electrostatic and nonpolar interactions places the protein in the stretched state, when each component force is out of equilibrium. Theories describing viscoelasticity of the protein-water interface are required to understand both the unusual protein conductivity and protein mobility. This proposal suggests a number of ways to unify the effect of complex dynamics of the protein-water interface with complex statistics of fluctuations to develop quantitative theories for a number of phenomena fundamental to protein function and molecular biophysics. Intellectual Merit: The proposed work develops formal theories and computational algorithms to address the general problem of nonergodic sampling in proteins and provides direct links to the laboratory experiment. The following research goals will be pursued: (1) The development of a theory of singlemolecule conductivity in proteins. This is a collaborative research with the experimental team responsible for the discovery of this novel phenomenon. (2) Theory of protein translational and rotational diffusivity in terms of competing forces producing stochastic translations and rotations. The theory will build on our current effort to develop models of protein dielectrophoresis to establish practical approaches to protein mobility in general. (3) An analytical theory of nonergodic sampling and violation of the FDT in proteins. We will address the problem of charge fluctuations in proteins by combining atomistic simulations with Monte Carlo sampling to establish the origin of average fractional protein charge. (4) A theory of protein electroelasticity will be developed in terms of frequency dependent viscoelastic moduli and solvation of the ionizable surface residues. The theory will provide memory functions for describing complex dynamics of protein diffusivity and the general problem of protein stability and fluctuations under the opposing action of electrostatic and nonpolar protein-water interactions. Broader Impact: The proposed research will relate to many fundamental and technological applications of protein science including protein separation techniques, the catalytic effect of enzymes, and singlemolecule conductivity to monitor protein function. Theoretical advances within this research agenda are already affecting the development of new technologies. The PI has an established track record of involving high-school students in research in molecular biophysics and will continue this activity if circumstances allow. The PIs group is involved in a number of collaborations with experimental colleagues and this practice will be continued in this project. Dissemination of research results will continue through publications and review articles reaching out to researches outside the immediate PIs expertise. As a part of this outreach, the PI plans to write a book during this funding cycle. 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.
Effective start/end date5/15/224/30/25


  • National Science Foundation (NSF): $510,000.00


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