Abstracts
Short talk 2: A Multi-Scale View of Multicomponent IDP Condensates from Simulation and Experiment
Miloš Ivanović
University of Zurich, Biochemistry, Winterthurerstrasse 190, 8057 Zurich [CH], m.ivanovic@bioc.uzh.ch
Author(s):
Miloš Ivanović, Nicola Galvanetto, Aritra Chowdhury, Robert Best, Benjamin Schuler
Condensates assembled from IDPs govern myriad cellular processes, but the principles linking molecular motions to emergent material properties remain poorly understood. Combining single-molecule FRET and multi-million–atom explicit-solvent simulations, we show that condensates of oppositely charged IDPs retain sub-microsecond chain reconfiguration and pico- to nanosecond side-chain exchange despite high viscosity [1]. Extending this experiment–simulation approach [2, 3] to multicomponent condensates spanning diverse sequences and salt concentrations, we identify striking correlations between viscosity, translational diffusion, and chain dynamics [4]. Simulations recapitulate these trends and reveal that sequence- and salt-dependent inter-residue contact lifetimes govern the effective friction linking molecular and macroscopic scales, in line with both polymer-physics models and independent measurements. Rapid exchange of charged interaction partners at high residue densities may represent a general mechanism by which molecules avoid dynamic arrest in the highly charged environment of the cell nucleus. Finally, we developed and validated a tailored strategy to refine force-field parameters for condensates and benchmark complementary routes, providing a toolkit for predictive simulations.
[1] Galvanetto*, Ivanović*, et al., Nature (2023)
[2] Nettels et al., Nat. Rev. Phys. (2024)
[3] Ivanović & Best, Curr. Opin. Struct. Biol. (2025)
[4] Galvanetto*, Ivanović*, et al., PNAS (2025)