Integrative Multiscale Modelling of Protein Dynamics in Complex Environments – ProDiCE

A fundamental goal of biophysical chemistry is to understand how physiological environments modulate the dynamics of proteins and, consequently, their function. In particular, we are interested in cellular membraneless organelles (MLOs). MLOs are delineated by liquid-liquid phase separation, often involving Intrinsically Disordered Proteins (IDPs), dynamic peptides that do not possess a well-defined folded structure but are nevertheless functional. MLOs can recruit specific biomolecules (clients), sometimes in response to environmental cues, and coordinate and optimise specific biochemical reactions. However, little is known about the role of dynamics in the recruitment and activity of clients. Our project aims to integrate multiple experimental techniques, such as NMR spectroscopy and small-angle scattering, with coarse-grained simulation approaches to advance our understanding of the composition rules and functional mechanisms of MLOs.