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PresentationsComputer modeling of the DNA-stabilizing protein Dps of the bacterium Escherichia coli with DNA of different lengthsSemenov Federal Research Center for Chemical Physics, Russian Academy of Sciences One of the most important proteins of bacteria and archaea under stress conditions is the DNA-binding protein Dps (DNA-binding protein from starved cells) [1]. It is a homologue of ferritin, spherical in shape with a cavity inside. The main functions of Dps Escherichia coli: sequestration of Fe2+ to prevent the Fenton reaction and preservation of DNA by forming co-crystals and DNA-Dps complexes during the stationary phase of bacterial culture growth [2]. Despite a large number of works in this area, the molecular mechanisms and type of DNA binding to the Dps protein are still unclear. Therefore, the aim of this work was to study E. coli Dps crystals with DNA molecules of different lengths and compositions using molecular dynamics and thermodynamic integration methods. The simulations were performed using the GROMACS package in the MARTINI force field according to the protocols developed in [3]. It was shown that DNA binding to Dps depends on the shape and size of the protein crystal, the length and composition of the DNA, and the ionic strength of the solution. A solution with an ion concentration corresponding to the cytoplasm of E. coli may be more favorable for DNA binding in DNA-protein complexes, and with a low ionic strength - for cocrystallization. Long-chain DNA molecules are adsorbed on the formed Dps crystals unevenly. Cocrystallization of DNA with Dps promotes the formation of symmetrical forms in nanocrystals. The binding affinity to the Dps surface is higher for regions of genomic DNA that have the highest specificity for the Dps protein. The computations were performed on MVS-10P at the Joint Supercomputer Center of the Russian Academy of Sciences. The work was carried out within the framework of the state assignment of the Ministry of Education and Science. References 1. Almirón M., Link A.J., Furlong D., Kolter R. A novel DNA-binding protein with regulatory and protective roles in starved Escherichia coli // Genes Dev. 6, 1992. 2646-2654. https://doi.org/10.1101/gad.6.12b.2646 2. Williams SM, Chatterji D. An Overview of Dps: Dual Acting Nanovehicles in Prokaryotes with DNA Binding and Ferroxidation Properties // Subcell Biochem. 96, 2021. 177-216. https://doi.org/10.1007/978-3-030-58971-4_3 3. Tereshkin, E. V., Tereshkina, K. B., Krupyanskii, Y. F. Predicting Binding Free Energies for DPS Protein-DNA Complexes and Crystals Using Molecular Dynamics. // Supercomputing Frontiers and Innovations. 9, 2, 2022. 33–45. https://doi.org/10.14529/jsfi220203
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