Disordered Proteins Across Scales: From Single-Chain Ensembles to Biomolecular Condensates

Speaker: Tatiana Morozova (École Normale Supérieure de Lyon)

Abstract:

The phase separation of intrinsically disordered proteins (IDPs) into biomolecular condensates plays an important role in cellular organisation and function and provides inspiration for the design of responsive biomaterials. Yet, connecting the conformational behaviour of individual disordered chains to their collective assembly remains a major challenge for molecular simulations.

In this talk, I will discuss how molecular simulations at different resolutions can bridge these scales. Using elastin-like polypeptides (ELPs), I will first show how sequence length modulates single-chain conformations and manifests in different aggregate states of elastin condensates. Next, using β-casein as an example, I will demonstrate how the same disordered protein can exhibit distinct polymeric regimes—from coil-like to globule-like states—across its free-energy landscape, highlighting the complexity of describing IDP conformational ensembles. Finally, I will move from single chains to many-chain systems and discuss how explicit-solvent coarse-grained simulations with the Martini force field enable access to biomolecular condensates. I will show how recent refinements of the model improve the description of IDPs in dilute solution and examine to what extent this improvement translates into an accurate description of their condensed phases.

This seminar will take place in room C3.011