Sequence and length-scale dependent dynamics in biocondensates of highly charged disordered proteins
Year: 2026
Type: article
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. Highly-charged intrinsically disordered proteins (IDPs) underpin biomolecular condensate formation, however, the influence of charge sequences on the dynamics within the condensate phase remains underexplored. Here, the authors use molecular dynamics simulations with explicit hydrodynamics and electrostatics to study the dynamics in IDP condensates across different length and time scales by varying the charge sequences of the constituent IDPs, showing that hydrodynamic and electrostatic effects are strongly coupled to the IDP charge sequence, in contrast with the expectation of long-range interactions being heavily screened.
Source: Communications Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,690
OpenAlex ID: W7125376107