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Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water

https://doi.org/10.1126/science.aan5774
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What this work says

Outgoing claims: the papers this work cites, builds on, or argues with.

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The Levinthal paradox of the interactome
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Slow formation of aggregation‐resistant β‐sheet folding intermediates
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SANS from homogeneous polymer mixtures: A unified overview
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Accurate SAXS Profile Computation and its Assessment by Contrast Variation Experiments
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Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response
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ATP-Independent Control of Autotransporter Virulence Protein Transport via the Folding Properties of the Secreted Protein
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Early Collapse is not an Obligate Step in Protein Folding
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Mapping the Folding Free Energy Surface for Metal-free Human Cu,Zn Superoxide Dismutase
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Fully Reduced Ribonuclease A Does not Expand at High Denaturant Concentration or Temperature
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Small-Angle X-ray Scattering of Reduced Ribonuclease A: Effects of Solution Conditions and Comparisons with a Computational Model of Unfolded Proteins
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Evidence for Initial Non-specific Polypeptide Chain Collapse During the Refolding of the SH3 Domain of PI3 Kinase
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Time-Resolved Small-Angle X-ray Scattering Study of the Folding Dynamics of Barnase
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Small-Angle X-ray Scattering and Single-Molecule FRET Spectroscopy Produce Highly Divergent Views of the Low-Denaturant Unfolded State
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Microsecond Barrier-Limited Chain Collapse Observed by Time-Resolved FRET and SAXS
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How, when and why proteins collapse: the relation to folding
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Assessing the accuracy of physical models used in protein-folding simulations: quantitative evidence from long molecular dynamics simulations
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Relating sequence encoded information to form and function of intrinsically disordered proteins
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The Statistical Conformation of a Highly Flexible Protein: Small-Angle X-Ray Scattering of S. aureus Protein A
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An Adequate Account of Excluded Volume Is Necessary To Infer Compactness and Asphericity of Disordered Proteins by Förster Resonance Energy Transfer
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Collapse Precedes Folding in Denaturant-Dependent Assembly of Ubiquitin
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TonB-Dependent Transporter FhuA in Planar Lipid Bilayers: Partial Exit of Its Plug from the Barrel
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Molecular-weight Determination by Light Scattering.
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Slow Unfolded-State Structuring in Acyl-CoA Binding Protein Folding Revealed by Simulation and Experiment
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Consistent View of Polypeptide Chain Expansion in Chemical Denaturants from Multiple Experimental Methods
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Static scattering function for a polymer chain in a good solvent
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The burst phase in ribonuclease A folding and solvent dependence of the unfolded state
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Chain collapse can occur concomitantly with the rate-limiting step in protein folding.
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Collapse transition in proteins
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Random-coil behavior and the dimensions of chemically unfolded proteins
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Pertactin β-helix folding mechanism suggests common themes for the secretion and folding of autotransporter proteins
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Characterizing the unfolded states of proteins using single-molecule FRET spectroscopy and molecular simulations
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Polymer scaling laws of unfolded and intrinsically disordered proteins quantified with single-molecule spectroscopy
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Benchmarking all-atom simulations using hydrogen exchange
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Random coil negative control reproduces the discrepancy between scattering and FRET measurements of denatured protein dimensions
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Prediction of protein antigenic determinants from amino acid sequences.
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PISCES: a protein sequence culling server
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WAXSiS: a web server for the calculation of SAXS/WAXS curves based on explicit-solvent molecular dynamics
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Static-coherent-scattering function for a single polymer chain: Conformational space renormalization of polymers. V
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Fast and accurate algorithms for protein side-chain packing
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Rapid calculation of side chain packing and free energy with applications to protein molecular dynamics

What points at this work

Incoming claims: where this work appears in other papers’ reference lists and arguments.

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A Metastable Contact and Structural Disorder in the Estrogen Receptor Transactivation Domain
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Life and death of Yfh1: how cool is cold denaturation
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The Cold-Unfolded State Is Expanded but Contains Long- and Medium-Range Contacts and Is Poorly Described by Homopolymer Models
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Denatured State Conformational Biases in Three-Helix Bundles Containing Divergent Sequences Localize near Turns and Helix Capping Residues
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Residual Structure in the Denatured State of the Fast-Folding UBA(1) Domain from the Human DNA Excision Repair Protein HHR23A
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Binding Affinity and Function of the Extremely Disordered Protein Complex Containing Human Linker Histone H1.0 and Its Chaperone ProTα
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Computational Prediction of Coiled–Coil Protein Gelation Dynamics and Structure
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Accelerated Missense Mutation Identification in Intrinsically Disordered Proteins Using Deep Learning
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Heterogeneity in Protein Folding and Unfolding Reactions
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Maximum Entropy Optimized Force Field for Intrinsically Disordered Proteins
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A Data-Driven Hydrophobicity Scale for Predicting Liquid–Liquid Phase Separation of Proteins
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Small-Angle X-ray Scattering Signatures of Conformational Heterogeneity and Homogeneity of Disordered Protein Ensembles
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Salt-Induced Transitions in the Conformational Ensembles of Intrinsically Disordered Proteins
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Interpreting Transient Interactions of Intrinsically Disordered Proteins
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The Analytical Flory Random Coil Is a Simple-to-Use Reference Model for Unfolded and Disordered Proteins
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A Stickiness Scale for Disordered Proteins
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Origin of Internal Friction in Disordered Proteins Depends on Solvent Quality
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Cell Volume Controls Protein Stability and Compactness of the Unfolded State
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Nature’s Shortcut to Protein Folding
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Sequence Effects on Size, Shape, and Structural Heterogeneity in Intrinsically Disordered Proteins
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Hydropathy Patterning Complements Charge Patterning to Describe Conformational Preferences of Disordered Proteins
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Revealing the Hidden Sensitivity of Intrinsically Disordered Proteins to their Chemical Environment
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Fundamental Challenges and Outlook in Simulating Liquid–Liquid Phase Separation of Intrinsically Disordered Proteins
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Resolving Site-Specific Heterogeneity of the Unfolded State under Folding Conditions
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The Role of Transient Intermediate Structures in the Unfolding of the Trp-Cage Fast-Folding Protein: Generating Ensembles from Time-Resolved X-ray Solution Scattering with Genetic Algorithms
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Alleviated Inhibition of Single Enzyme in Confined and Crowded Environment
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Evolution of All-Atom Protein Force Fields to Improve Local and Global Properties
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Complete Diagram of Conformational Regimes for Polyampholytic Disordered Proteins
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Manifold of Polyampholyte Necklaces: From Charge Migration to Hierarchical Structure
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Conformational Ensembles of an Intrinsically Disordered Protein Consistent with NMR, SAXS, and Single-Molecule FRET
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Quantitative Description of Intrinsically Disordered Proteins Using Single-Molecule FRET, NMR, and SAXS
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The Protein Unfolded State: One, No One and One Hundred Thousand
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Nucleotide-Specific RNA Conformations and Dynamics as Precursors to Ribonucleoprotein Condensates
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Phosphoglycerate Kinase Can Adopt Topologically Misfolded Forms That Are More Stable Than Its Native State
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Protein Network Structure Enables Switching between Liquid and Gel States
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Mutations in Tau Protein Promote Aggregation by Favoring Extended Conformations
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Identifying Sequence Effects on Chain Dimensions of Disordered Proteins by Integrating Experiments and Simulations
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Dynamical Buffering of Reconfiguration Dynamics in Intrinsically Disordered Proteins
inferred← citeshttps://doi.org/10.1038/s41467-022-32874-0openalex-snapshot
Protein structural transitions critically transform the network connectivity and viscoelasticity of RNA-binding protein condensates but RNA can prevent it
inferred← citeshttps://doi.org/10.1038/s41467-022-35370-7openalex-snapshot
Condensates formed by prion-like low-complexity domains have small-world network structures and interfaces defined by expanded conformations
inferred← citeshttps://doi.org/10.1038/s41467-024-50647-9openalex-snapshot
Rescaling protein-protein interactions improves Martini 3 for flexible proteins in solution
inferred← citeshttps://doi.org/10.1038/s41467-024-51972-9openalex-snapshot
Cation-induced intramolecular coil-to-globule transition in poly(ADP-ribose)
inferred← citeshttps://doi.org/10.1038/s41467-024-53904-zopenalex-snapshot
p14ARF forms meso-scale assemblies upon phase separation with NPM1
inferred← citeshttps://doi.org/10.1038/s41557-021-00840-wopenalex-snapshot
Deciphering how naturally occurring sequence features impact the phase behaviours of disordered prion-like domains
inferred← citeshttps://doi.org/10.1038/s41565-020-00798-9openalex-snapshot
Structural and dynamics analysis of intrinsically disordered proteins by high-speed atomic force microscopy
inferred← citeshttps://doi.org/10.1038/s41573-021-00199-0openalex-snapshot
Advances in targeting ‘undruggable’ transcription factors with small molecules
inferred← citeshttps://doi.org/10.1038/s41580-023-00647-2openalex-snapshot
Mechanisms and pathology of protein misfolding and aggregation
inferred← citeshttps://doi.org/10.1038/s41580-023-00673-0openalex-snapshot
The molecular basis for cellular function of intrinsically disordered protein regions
inferred← citeshttps://doi.org/10.1038/s41586-024-07784-4openalex-snapshot
The ribosome lowers the entropic penalty of protein folding
inferred← citeshttps://doi.org/10.1038/s41586-024-08400-1openalex-snapshot
The sequence–structure–function relationship of intrinsic ERα disorder
inferred← citeshttps://doi.org/10.1038/s41586-026-10141-2openalex-snapshot
Accurate predictions of disordered protein ensembles with STARLING
inferred← citeshttps://doi.org/10.1038/s41586-026-10849-1openalex-snapshot
Rational design of disordered proteins for sequence–function investigation
inferred← citeshttps://doi.org/10.1038/s41592-023-02159-5openalex-snapshot
Direct prediction of intrinsically disordered protein conformational properties from sequence
inferred← citeshttps://doi.org/10.1038/s41592-026-03003-2openalex-snapshot
Toward a unified framework for determining conformational ensembles of disordered proteins
inferred← citeshttps://doi.org/10.1038/s41598-020-58868-wopenalex-snapshot
The Order-Disorder Continuum: Linking Predictions of Protein Structure and Disorder through Molecular Simulation
inferred← citeshttps://doi.org/10.1038/s42003-021-01759-1openalex-snapshot
Full structural ensembles of intrinsically disordered proteins from unbiased molecular dynamics simulations
inferred← citeshttps://doi.org/10.1038/s42003-025-09395-9openalex-snapshot
Parkinson’s disease-specific α-Synuclein variants potentially drive Lewy body formation by engaging in promiscuous and non-functional interactions
inferred← citeshttps://doi.org/10.1039/bk9781839165986-00278openalex-snapshot
Probing Single Chaperone Substrates
inferred← citeshttps://doi.org/10.1039/c7cp04546hopenalex-snapshot
Comment on “Thermal compaction of the intrinsically disordered protein tau: entropic, structural, and hydrophobic factors” by A. Battisti, G. Ciasca, A. Grottesi and A. Tenenbaum, Phys. Chem. Chem. Phys. , 2017, 19 , 8435
inferred← citeshttps://doi.org/10.1039/d4nr03375bopenalex-snapshot
Determination of absolute intramolecular distances in proteins using anomalous X-ray scattering interferometry
inferred← citeshttps://doi.org/10.1063/1.5006954openalex-snapshot
Inferring properties of disordered chains from FRET transfer efficiencies
inferred← citeshttps://doi.org/10.1063/1.5078615openalex-snapshot
The combined force field-sampling problem in simulations of disordered amyloid-β peptides
inferred← citeshttps://doi.org/10.1063/4.0000180openalex-snapshot
Deep mining of the protein energy landscape
inferred← citeshttps://doi.org/10.1063/5.0176306openalex-snapshot
Fine structures of intrinsically disordered proteins
inferred← citeshttps://doi.org/10.1063/5.0307183openalex-snapshot
In search of shape in the unshaped: Constructing ensembles of intrinsically disordered proteins
inferred← citeshttps://doi.org/10.1073/pnas.1804177115openalex-snapshot
Relation between single-molecule properties and phase behavior of intrinsically disordered proteins
inferred← citeshttps://doi.org/10.1073/pnas.1813038116openalex-snapshot
Commonly used FRET fluorophores promote collapse of an otherwise disordered protein
inferred← citeshttps://doi.org/10.1073/pnas.1818206116openalex-snapshot
Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions
inferred← citeshttps://doi.org/10.1073/pnas.1904813116openalex-snapshot
Effective concentrations enforced by intrinsically disordered linkers are governed by polymer physics
inferred← citeshttps://doi.org/10.1073/pnas.1907251116openalex-snapshot
Generation of the configurational ensemble of an intrinsically disordered protein from unbiased molecular dynamics simulation
inferred← citeshttps://doi.org/10.1073/pnas.1913442117openalex-snapshot
Protein folding from heterogeneous unfolded state revealed by time-resolved X-ray solution scattering
inferred← citeshttps://doi.org/10.1073/pnas.2003773117openalex-snapshot
Properties of protein unfolded states suggest broad selection for expanded conformational ensembles
inferred← citeshttps://doi.org/10.1073/pnas.2109169119openalex-snapshot
Lipid bilayer induces contraction of the denatured state ensemble of a helical-bundle membrane protein
inferred← citeshttps://doi.org/10.1073/pnas.2111696118openalex-snapshot
Accurate model of liquid–liquid phase behavior of intrinsically disordered proteins from optimization of single-chain properties
inferred← citeshttps://doi.org/10.1073/pnas.2220180120openalex-snapshot
Intramolecular structural heterogeneity altered by long-range contacts in an intrinsically disordered protein
inferred← citeshttps://doi.org/10.1073/pnas.2221286120openalex-snapshot
Intrinsic disorder and conformational coexistence in auxin coreceptors
inferred← citeshttps://doi.org/10.1073/pnas.2313835120openalex-snapshot
Glutamine-rich regions of the disordered CREB transactivation domain mediate dynamic intra- and intermolecular interactions
inferred← citeshttps://doi.org/10.1073/pnas.2321606121openalex-snapshot
HDX–MS finds that partial unfolding with sequential domain activation controls condensation of a cellular stress marker
inferred← citeshttps://doi.org/10.1073/pnas.2409139121openalex-snapshot
Molecular insights into the interaction between a disordered protein and a folded RNA
inferred← citeshttps://doi.org/10.1073/pnas.2415220121openalex-snapshot
A genetically encoded anomalous SAXS ruler to probe the dimensions of intrinsically disordered proteins
inferred← citeshttps://doi.org/10.1073/pnas.2425999122openalex-snapshot
Identification of an on-pathway intermediate illuminates the kinetic competition between protein folding and misfolding
inferred← citeshttps://doi.org/10.1088/2399-1984/abfb7copenalex-snapshot
Intrinsically disordered proteins at the nano-scale
inferred← citeshttps://doi.org/10.1093/nar/gkab063openalex-snapshot
Interplay of folded domains and the disordered low-complexity domain in mediating hnRNPA1 phase separation
inferred← citeshttps://doi.org/10.1093/pnasnexus/pgae006openalex-snapshot
Dynamic conformational changes of a tardigrade group-3 late embryogenesis abundant protein modulate membrane biophysical properties
inferred← citeshttps://doi.org/10.1093/pnasnexus/pgaf039openalex-snapshot
Intrinsic stiffness and Θ -solvent regime in intrinsically disordered proteins: Implications for liquid–liquid phase separation
inferred← citeshttps://doi.org/10.1093/protein/gzz014openalex-snapshot
Information theoretic measures for quantifying sequence–ensemble relationships of intrinsically disordered proteins
inferred← citeshttps://doi.org/10.1098/rsif.2018.0244openalex-snapshot
Lessons from pressure denaturation of proteins
inferred← citeshttps://doi.org/10.1101/2020.02.05.935890openalex-snapshot
Integrating multiple experimental data to determine conformational ensembles of an intrinsically disordered protein
inferred← citeshttps://doi.org/10.1101/2020.06.25.171116openalex-snapshot
Order and disorder – an integrative structure of the full-length human growth hormone receptor
inferred← citeshttps://doi.org/10.1101/2020.07.06.189613openalex-snapshot
Beta turn propensity and a model polymer scaling exponent identify disordered proteins that phase separate
inferred← citeshttps://doi.org/10.1101/2021.03.05.434111openalex-snapshot
RNA modulation of transport properties and stability in phase separated condensates
inferred← citeshttps://doi.org/10.1101/2022.05.21.492916openalex-snapshot
Condensates of disordered proteins have small-world network structures and interfaces defined by expanded conformations
inferred← citeshttps://doi.org/10.1101/2022.06.11.495732openalex-snapshot
Assessment of models for calculating the hydrodynamic radius of intrinsically disordered proteins
inferred← citeshttps://doi.org/10.1101/2022.09.21.508844openalex-snapshot
Sequential Activation and Local Unfolding Control Poly(A)-Binding Protein Condensation
inferred← citeshttps://doi.org/10.1101/2022.10.31.514552openalex-snapshot
Generation of Unfolded Outer Membrane Protein Ensembles Targeted by Hydrodynamic Properties
inferred← citeshttps://doi.org/10.1101/2022.11.14.516525openalex-snapshot
Interpreting transient interactions of intrinsically disordered proteins
inferred← citeshttps://doi.org/10.1101/2023.08.06.552128openalex-snapshot
Conserved molecular recognition by an intrinsically disordered region in the absence of sequence conservation
inferred← citeshttps://doi.org/10.1101/2023.10.25.564012openalex-snapshot
Length-dependent Intramolecular Coil-to-Globule Transition in Poly(ADP-ribose) Induced by Cations
inferred← citeshttps://doi.org/10.1101/2023.10.29.564547openalex-snapshot
Rational design of disordered proteins for systematic sequence-to-function investigation
inferred← citeshttps://doi.org/10.1101/2024.02.09.579681openalex-snapshot
Determination of Absolute Intramolecular Distances in Proteins by Anomalous X-ray Scattering Interferometry
inferred← citeshttps://doi.org/10.1101/2025.02.06.636987openalex-snapshot
Nucleotide-specific RNA conformations and dynamics within ribonucleoprotein condensates
inferred← citeshttps://doi.org/10.1101/2025.02.26.640428openalex-snapshot
Nanometer condensate organization in live cells derived from partitioning measurements
inferred← citeshttps://doi.org/10.1101/2025.07.03.663089openalex-snapshot
Hydration free energy is a significant predictor of globular protein incorporation into condensates
inferred← citeshttps://doi.org/10.1101/2025.10.19.683306openalex-snapshot
AF-CALVADOS: AlphaFold-guided simulations of multi-domain proteins at the proteome level
inferred← citeshttps://doi.org/10.1107/s0108767319095916openalex-snapshot
The importance of measuring the solvent quality of unfolded proteins
inferred← citeshttps://doi.org/10.1107/s1600576723011019openalex-snapshot
BioXTAS RAW 2 : new developments for a free open-source program for small-angle scattering data reduction and analysis
inferred← citeshttps://doi.org/10.1126/sciadv.abh3805openalex-snapshot
Order and disorder—An integrative structure of the full-length human growth hormone receptor
inferred← citeshttps://doi.org/10.1126/sciadv.abl6293openalex-snapshot
Protein chain collapse modulation and folding stimulation by GroEL-ES
inferred← citeshttps://doi.org/10.1126/sciadv.adm9926openalex-snapshot
Design of intrinsically disordered protein variants with diverse structural properties
inferred← citeshttps://doi.org/10.1126/science.aar7101openalex-snapshot
Comment on “Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water”
inferred← citeshttps://doi.org/10.1126/science.aar7949openalex-snapshot
Response to Comment on “Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water”
inferred← citeshttps://doi.org/10.1126/science.aat0958openalex-snapshot
Response to Comment on “DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification”
inferred← citeshttps://doi.org/10.1126/science.aau8230openalex-snapshot
Comment on “Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water”
inferred← citeshttps://doi.org/10.1126/science.aaw8653openalex-snapshot
Valence and patterning of aromatic residues determine the phase behavior of prion-like domains
inferred← citeshttps://doi.org/10.1126/science.adq8381openalex-snapshot
Sequence-based prediction of intermolecular interactions driven by disordered regions
inferred← citeshttps://doi.org/10.1140/epje/s10189-023-00360-0openalex-snapshot
Pincus blob elasticity in an intrinsically disordered protein
inferred← citeshttps://doi.org/10.1140/epje/s10189-023-00383-7openalex-snapshot
Electrostatics and hydrophobicity in the dynamics of intrinsically disordered proteins
inferred← citeshttps://doi.org/10.1140/epje/s10189-024-00409-8openalex-snapshot
From isolated polyelectrolytes to star-like assemblies: the role of sequence heterogeneity on the statistical structure of the intrinsically disordered neurofilament-low tail domain
inferred← citeshttps://doi.org/10.1146/annurev-biophys-070317-032838openalex-snapshot
Collapse Transitions of Proteins and the Interplay Among Backbone, Sidechain, and Solvent Interactions
inferred← citeshttps://doi.org/10.1146/annurev-biophys-080124-123012openalex-snapshot
Collapse and Protein Folding: Should We Be Surprised That Biothermodynamics Works So Well?
inferred← citeshttps://doi.org/10.1146/annurev-biophys-120221-095357openalex-snapshot
Rules of Physical Mathematics Govern Intrinsically Disordered Proteins
inferred← citeshttps://doi.org/10.1146/annurev-physchem-071819-113553openalex-snapshot
Biomolecular Phase Separation: From Molecular Driving Forces to Macroscopic Properties
inferred← citeshttps://doi.org/10.11606/d.43.2020.tde-24032020-120700openalex-snapshot
Determinação da estrutura e do estado oligomérico de proteínas chaperonas por espalhamento de raios-x a baixos ângulos (SAXS)
inferred← citeshttps://doi.org/10.1186/s43556-022-00075-2openalex-snapshot
Post-translational modifications in liquid-liquid phase separation: a comprehensive review
inferred← citeshttps://doi.org/10.13070/mm.en.9.2794openalex-snapshot
Biological Condensates
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