Polyubiquitin chains are flexible multidomain proteins, whose conformational dynamics enable them to regulate multiple biological pathways. Their dynamic is determined by the linkage between ubiquitins and by the number of ubiquitin units. Characterizing polyubiquitin behavior as a function of their length is hampered because of increasing system size and conformational variability. Here, we introduce a new approach to efficiently integrating small-angle x-ray scattering with simulations allowing us to accurately characterize the dynamics of linear di-, tri-, and tetraubiquitin in the free state as well as of diubiquitin in complex with NEMO, a central regulator in the NF-kB pathway. Our results show that the behavior of the diubiquitin subunits is independent of the presence of additional ubiquitin modules and that the dynamics of polyubiquitins with different lengths follow a simple model. Together with experimental data from multiple biophysical techniques, we then rationalize the 2:1 NEMO:polyubiquitin binding.
We have been awarded a grant for a collaboration lead by Stefano Casola (IFOM) to work on the “Joint artificial intelligence and protein structure modelling to guide large-scale screenings for anti-SARS-Cov2 neutralizing antibodies”. The network includes Giulia Marchetti (UNIMI), Raffaele Badolato (UNIBS), Maria Rodriguez Martinez (IBM, Zurich)
We have been awarded a PRACE grant with an allocation of 68M hours on Piz Daint (CSCS) to apply our recently developed multi-resolution SAXS strategy to characterize the structure and dynamics of multiple Light-Chain variants.
This is Cristina latest work: SAXS experiments provide low-resolution but valuable information about the dynamics of biomolecular systems, which could be ideally integrated into molecular dynamics (MD) simulations to accurately determine conformational ensembles of flexible proteins. The applicability of this strategy is hampered by the high computational cost required to calculate scattering intensities from three-dimensional structures. We previously presented a hybrid resolution method that makes atomistic SAXS-restrained MD simulation feasible by adopting a coarse-grained approach to efficiently back-calculate scattering intensities; here, we extend this technique, applying it in the framework of metainference with the aim to investigate the dynamical behavior of flexible biomolecules. The efficacy of the method is assessed on the K63-diubiquitin, showing that the inclusion of SAXS restraints is effective in generating a reliable conformational ensemble, improving the agreement with independent experimental data.
Federico has discussed his thesis on the molecular recognition between MHC-I and TCR graduating with 110/110, congratulations!
We have been awarded a “Transition Grant – Horizon 2020” from the University of Milano to try to strengthen our projects in the field of protein aggregation!
Danny is visiting us this week in the context of our collaborative project funded by the Ministry of Science and Technology, Taiwan (Grant number MOST 107-2628-M-001-005-MY3).
Welcome to Shadi, a new undergrad student joining us!
Carlo is attending the XX Telethon convention, still too early to present the results of our hERG project! Looking forward for the next conventions for that!
Francesco has successfully discussed his master thesis on in silicon and in vitro characterisation of light-chain dynamics today! Shortly he is moving for a PhD in Copenhagen in the group of Krensten Lindorff-Larsen