ArticlePLoS computational biology2021
Targeted modulation of protein liquid-liquid phase separation by evolution of amino-acid sequence.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 40 citations in OpenAlex.
- De novo design of peptides localizing at the interface of biomolecular condensates.Nature communications · 2026Article
- A composition-matching algorithm, MatchIDR, identifies prion-like domains that localize to stress granules.Protein science : a publication of the Protein Society · 2026Article
- Liquid-liquid phase separation mediated immune evasion of respiratory syncytial virus against oligoadenylate synthetase-RNase L pathway.PLoS pathogens · 2026Article
- Correlated Segments of Intrinsically Disordered Proteins as Drivers of Homotypic Phase Separation.JACS Au · 2025Article
- Controlled liquid-liquid phase separation via the simulation-guided, targeted engineering of the RNA-binding protein PARCL.iScience · 2025Article
- An Analysis of Intrinsic Protein Disorder in Antimicrobial Peptides.The protein journal · 2025Article
- Modeling biomolecular condensates across scales: Atomistic, coarse-grained, and data-driven approaches.Advances in physics: X · 2025Article
- Design of intrinsically disordered protein variants with diverse structural properties.Science advances · 2024Article
- Fundamental Aspects of Phase-Separated Biomolecular Condensates.Chemical reviews · 2024Review
- Aromatic and arginine content drives multiphasic condensation of protein-RNA mixtures.Biophysical journal · 2024Article
- When Data Are Lacking: Physics-Based Inverse Design of Biopolymers Interacting with Complex, Fluid Phases.Journal of chemical theory and computation · 2024Review
- Sequence-ensemble-function relationships for disordered proteins in live cells.bioRxiv : the preprint server for biology · 2023Article
- Design of intrinsically disordered protein variants with diverse structural properties.bioRxiv : the preprint server for biology · 2023Article
- Proximity to criticality predicts surface properties of biomolecular condensates.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Thermodynamic origins of two-component multiphase condensates of proteins.Chemical science · 2023Article
- Physics-driven coarse-grained model for biomolecular phase separation with near-quantitative accuracy.Nature computational science · 2021Article
- Valency and Binding Affinity Variations Can Regulate the Multilayered Organization of Protein Condensates with Many Components.Biomolecules · 2021Article
- Single-Molecule Microscopy Meets Molecular Dynamics Simulations for Characterizing the Molecular Action of Proteins on DNA and in Liquid Condensates.Frontiers in molecular biosciences · 2021Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rationally and efficiently modifying the amino-acid sequence of proteins to control their ability to undergo liquid-liquid phase separation (LLPS) on demand is not only highly desirable, but can also help to elucidate which protein features are important for LLPS. Here, we propose a computational method that couples a genetic algorithm to a sequence-dependent coarse-grained protein model to evolve the amino-acid sequences of phase-separating intrinsically disordered protein regions (IDRs), and purposely enhance or inhibit their capacity to phase-separate. We validate the predicted critical solution temperatures of the mutated sequences with ABSINTH, a more accurate all-atom model. We apply the algorithm to the phase-separating IDRs of three naturally occurring proteins, namely FUS, hnRNPA1 and LAF1, as prototypes of regions that exist in cells and undergo homotypic LLPS driven by different types of intermolecular interaction, and we find that the evolution of amino-acid sequences towards enhanced LLPS is driven in these three cases, among other factors, by an increase in the average size of the amino acids. However, the direction of change in the molecular driving forces that enhance LLPS (such as hydrophobicity, aromaticity and charge) depends on the initial amino-acid sequence. Finally, we show that the evolution of amino-acid sequences to modulate LLPS is strongly coupled to the make-up of the medium (e.g. the presence or absence of RNA), which may have significant implications for our understanding of phase separation within the many-component mixtures of biological systems.
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