Abstract
Highly-charged intrinsically disordered proteins (IDPs) underpin biomolecular condensate formation through liquid–liquid phase separation, yet the influence of charge sequences on the dynamics within the condensate phase remains poorly understood. Using extensive molecular dynamics simulations with explicit hydrodynamics and electrostatics, we study the dynamics in IDP condensates across different length and time scales, by systematically varying the charge sequences of the constituent IDPs. Contrary to the expectation that long-range interactions are heavily screened in dense semidilute polymer solutions, we find hydrodynamics and electrostatics significantly influence the dynamics in IDP condensates and their effects are strongly coupled to the charge sequence of the constituent IDPs. For condensates of low to intermediate-κ IDPs, where κ is a measure of the charge blockiness of the charge sequence, we find hydrodynamics dominates the dynamics up to the length scale of the chain and beyond. On the sub-chain level, segmental relaxation is highly coupled to intra-chain electrostatic correlations due to local charge patterns, where sections with more charge-balanced blocks have faster relaxation. Furthermore, the viscosity in IDP condensates is significantly length-scale-dependent, with condensates of high-κ IDPs exhibiting large difference between microscopic and macroscopic viscosity. Such length-scale-dependent viscosity may be the key to understanding the experimentally observed extremely fast molecule-level dynamics in biocondensates of highly-charged IDPs. Our findings highlight the intricate relationship between charge sequences, hydrodynamics, and electrostatics in shaping the dynamics in IDP condensates at different length and time scales.
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All data are included in the article and/or in the Supplementary Information. Two binary files representing initial and final configurations of the simulation trajectories are uploaded in Figshare repository (https://doi.org/10.6084/m9.figshare.30653600). Other source data and codes are available from the corresponding author upon request.
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Acknowledgements
We thank the generous allocation of computational time from the HPC4 cluster in the Information Technology Services Center (ITSC) of HKUST. Funding: H. Zhou, Z. Wu and S. Chen thank the start-up funding from The Hong Kong University of Science and Technology (HKUST).
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Haoke Zhou: Methodology, Software, Investigation, Visualization, Writing—original draft. Zongpei Wu: Software. Lingxiang Jiang: Suggestion. Zhen-Gang Wang: Supervision, Writing— review and editing. Shensheng Chen: Conceptualization, Visualization, Supervision, Writing— review and editing, Funding acquisition.
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Communications Chemistry thanks Artem Rumyantsev and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. A peer review file is available.
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Zhou, H., Wu, Z., Jiang, L. et al. Sequence and length-scale dependent dynamics in biocondensates of highly charged disordered proteins. Commun Chem (2026). https://doi.org/10.1038/s42004-026-01903-0
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DOI: https://doi.org/10.1038/s42004-026-01903-0
