Intrinsically disordered proteins (IDPs) and disordered protein regions, which comprise over 40% of the eukaryotic proteome, exhibit complex dynamics, fluctuating between diverse conformational ensembles. Unlike structured proteins, where short-range interactions and long-range contacts dictate singular three-dimensional folding, IDPs lack a single stable structure. To understand their biological function, it is crucial to establish a correlation between the amino acid sequence and the statistical properties of their structural ensemble.In this talk, I will present our recent work on neurofilament proteins, which are essential neuronal-specific cytoskeletal components containing large intrinsically disordered domains. Our study spans multiple length scales—from nanoscopic to macroscopic—aiming to uncover the molecular mechanisms underlying their functional behavior. By leveraging coarse-grained polymer physics models and integrating minimal parameters, we demonstrate that the structural ensemble of neurofilament proteins can be reasonably predicted. However, our findings underscore that specific sequence motifs and the surrounding context are necessary to fully capture the protein’s conformational landscape in solution.These results highlight the power of advanced polymer theories in describing the ensemble behavior of IDPs, offering a promising avenue for modeling their function and dysfunction, particularly in neurodegenerative disease contexts. By bridging the gap between sequence specificity and polymer physics, we aim to establish a more comprehensive framework for predicting IDP behavior and its implications in health and disease.Students interested in meeting the speaker after the seminar may sign up here:LINKFOR THE LATEST UPDATES AND CONTENT ON SOFT MATTER AND BIOLOGICAL PHYSICS AT THE WEIZMANN, VISIT OUR WEBSITE: https://www.bio
