Keywords: Intrinsically disordered protein, Protein aggregation, Coarse-grained model, Molecular dynamics, High performance computing Internship Duration: 30/11/-1 - 30/11/-1
Head of the hosting team: Benoit Crousse and Sandrine Ongeri
Website: Click here
Address of the host laboratory: BioCIS - UMR 8076 Team FLUOPEPIT 5 rue Jean-Baptiste Clément 92290 Châtenay-Malabry France
Supervisor: Tâp Ha-DuongE-mail: tap.ha-duong@universite-paris-saclay.fr Phone: +33 1 46 83 57 38
Liquid-liquid phase separation (LLPS) of proteins is a biological process involved in the formation of membrane-less organelles such as nucleoli or stress granules. Proteins that undergo LLPS are generally intrinsically disordered proteins with low complexity regions composed of repeats of short motifs that are rich in glycine, proline, serine, or threonine. Due to their extreme flexibility, the structures of these proteins and of their aggregates are difficult to be characterized at the atomic scale by experiments. In that context, the project aims at investigating the aggregation properties of poly(amino acid)s with low complexity sequence by using molecular modeling techniques. More specifically, the work will consist in performing molecular dynamics simulations of coarse-grained models of poly(amino acid)s and to study their aggregation and dissolution processes as a function of the temperature, the pH, and the ionic strength of the aqueous solution.
Linux shell Molecular dynamics simulation (Gromacs) Python script Chimera, PyMol, and/or VMD Xmgrace and/or Gnuplot
[1] Alberti et al. Liquid–Liquid Phase Separation in Disease. Annu. Rev. Genet. 2019, 53, 171–194. [2] Cai et al. Biomolecular Condensates and Their Links to Cancer Progression. Trends Biochem. Sci. 2021, 1767, 1–15. [3] Babinchak et al. Small molecules as potent biphasic modulators of protein liquid-liquid phase separation. Nat. Commun. 2020, 11, 5574. [4] Wheeler R.J. Therapeutics: how to treat phase separation-associated diseases. Emerg. Top. Life Sci. 2020, 4, 331–342. [5] Molza et al. Simulations of the upper critical solution temperature behavior of poly(ornithine-cocitrulline)s using Martini-based coarse-grained force fields. J. Chem. Theory Comput. 2021, 17, 4499–4511.
