Protein-protein interactions in the purinosome metabolon
Metabolic enzymes form regulatory clusters in cells, the metabolons, where enzymes are spatially and temporally organized into multienzyme complexes. The goal of the project is to investigate by multi-scale computer simulations the structure, dynamics and ultimately function of a metabolon: the purinosome. The aim is to gain molecular insights into the control of the metabolic flux and its regulation in the purinosome, and possibly unravel novel therapeutic strategies. The computational investigation will be based on the innovative technique developed in the host laboratory, the lattice Boltzmann Molecular Dynamics, based on coarse-grained models for proteins combined to atomistic simulations. Software development will be carried out in collaboration with S. Melchionna (Lexma- Technology, Rome, Italy).
An, S., Kumar, R., Sheets, E.D., Benkovic, S.J., 2008. Reversible Compartmentalization of de novo Purine Biosynthetic Complexes in Living Cells. Science 320, 103–106
Sterpone, F., Derreumaux, P., Melchionna, S., 2015. Protein simulations in fluids: coupling the OPEP coarse-grained force field with hydrodynamics. J. Chem. Theory Comput. 11, 1843-1853.
Sterpone F., et al. 2014. The OPEP coarse-grained protein model: from single molecules, amyloid formation, role of macromolecular crowding and hydrodynamics to RNA/DNA complexes. Chem. Soc. Rev. 43, 4871-4893.
Timr, S., Gnutt, D., Ebbinghaus, S., Sterpone, F., 2020. The Unfolding Journey of Superoxide Dismutase 1 Barrels under Crowding: Atomistic Simulations Shed Light on Intermediate States and Their Interactions with Crowders, J. Phys. Chem. Lett. 11, 4206-421.
Timr, S., Sterpone, F., 2021. Stabilizing or Destabilizing: Simulations of Chymotrypsin Inhibitor 2 under Crowding Reveal Existence of a Crossover Temperature, J. Phys. Chem. Lett. 12, 1741-1746.
Gnutt, D., Timr, S., Ahlers, J., König, B., Manderfeld, E., Heyden, M., Sterpone, F., Ebbinghaus, S., 2019b. Stability Effect of Quinary Interactions Reversed by Single Point Mutations. J. Am. Chem. Soc.
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