Electrostatic interactions in biological systems
Zusammenfassung der Projektergebnisse
This project is focused on electrostatic interactions in biologically relevant soft matter systems. The main emphasis was on detailed description of electric charges ubiquitous on DNA molecules, protein-DNA surfaces, as well as on lipid membranes, concentrating on structure-mediated charge patterning effects. The strategy was to start from a precise modeling of constituents of the system in order to unravel the behavior in their complexes on larger scales. In particular, one subject of the proposal was to uncover the effect of internucleosomal interactions as the driving force for formation of 30 nm chromatin fibers. We employed the standard Poisson-Boltzmann theory for solving electrostatic problems, the classical elasticity theory for calculating the response of bent DNA-like elastic filaments, the concepts of deformation theory of liquid crystals, and some theoretical approaches for polyelectrolyte adsorption. We proposed several models to describe dense assemblies of DNA molecules, DNA complexes with proteins and oppositely charged membranes, as well as for protein-mediated DNA looping. For DNA cholesteric phases, we predicted a non-monotonic behavior of the cholesteric pitch on DNA lattice density, similar to that observed in experiments. For the lamellar DNA-membrane complexes in the presence of multivalent cations, we have shown that the DNA packing density is dictated by optimization of helicity-mediated DNA-DNA electrostatic energy. For DNA looping problems, the form and energetics of DNA loops predicted from the model was in agreement with the outcomes of recent extensive computer simulations and experimental data available. Some attention was also paid to theoretical modeling of DNA-DNA sequence recognition and DNA-DNA friction on nano-scale. In particular, we suggested that two identical DNAs in close parallel proximity exhibit more pronounced friction than two unrelated DNA sequences. This prediction can in principle be checked in single-molecule experiments on tight superhelical DNA plies. This DNA friction on base-pair level as well as DNA sequence recognition predicted by the theory for gene-relevant DNA homologues, can potentially contribute to DNA-DNA homologous pairing and gene shuffling in vivo. To underline the polyelectrolyte character of DNA, we proposed a model description of coil-to-globule collapse transition of highly-charged polyelectrolyte chains and formation of polyelectrolyte multilayers. For the latter, the response upon multilayer formation measured experimentally on the substrate surface of a bio-sensor appears to be in close agreement with the predictions of our electrostatic model. One of the main objectives was a deeper understanding of diffusion of DNA-binding proteins in a coil of DNA and unraveling the mechanisms of DNA-protein electrostatic recognition. For the first task, we proposed a simple non-equilibrium model that allowed to describe a puzzling phenomenon of facilitated diffusion of small DNA-binding proteins on long DNAs. For the second problem, we suggested a theoretical model akin to the known scenarios for DNA-DNA and protein-protein electrostatic recognition. We confirmed this mechanism later for a large class of vitally important structural proteins of pro- and eukaryotes via detailed analysis of charge patterns along the contact surfaces in many DNA- protein complexes, using their structural data available in the Protein Data Bank. Hopefully, this knowledge might provide us in the future with some control over binding and action of proteins on DNA.
Projektbezogene Publikationen (Auswahl)
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J. Phys. Chem. B, 111 7914 (2007)
A. G. Cherstvy
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J. Phys. Chem. B, 112 12585 (2008)
A. G. Cherstvy
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J. Phys. Chem. B, 112 4741 (2008)
A. G. Cherstvy, A. B. Kolomeisky, and A. A. Kornyshev
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J. Phys. Chem. B, 113 4242 (2009)
A. G. Cherstvy
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J. Phys. Chem. B, 113 5350 (2009)
A. G. Cherstvy
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J. Phys. Chem. B, 114 5241 (2010)
A. G. Cherstvy
