Seminar Tatiana Morozova & Fran Toplek (ENS Lyon – joint talk)

Disordered Proteins: Insights from Polymer Physics

The phase separation of intrinsically disordered proteins (IDPs), leading to the formation of biomolecular condensates, has attracted considerable attention because of its central role in cellular organisation and function, as well as its potential for biomaterial applications. Using state-of-the-art atomistic simulations, I will demonstrate that disordered proteins can exhibit markedly different polymer-like behaviours—ranging from coil-like to globule-like states—across different regions of their free-energy landscape, using β-casein as an example. In addition, by combining molecular dynamics simulations with quasi-elastic neutron scattering experiments, I will show how dense protein assemblies behave as self-crowded microenvironments that give rise to anomalous, non-Fickian diffusion and heterogeneous dynamics. These results provide molecular-level insight into how macromolecular organisation governs transport processes within biomolecular condensates. Finally, I will discuss strategies for extending simulations toward large-scale assemblies of IDPs using the coarse-grained force field.

Structure-Based Approaches to Data-Driven Protein Folding, Aggregation, and Self-Assembly

Multi-eGO is a data-informed modelling framework based on structure-based models with an added Bayesian touch. As a semi-transferable model, it can be applied to a variety of biomolecular systems whenever experimental or high-resolution molecular dynamics data are available, enabling the construction of simplified yet efficient force fields. This allows the study of assembly processes and out-of-equilibrium protein dynamics at quasi-atomic resolution and extended timescales.