Analytical Theory for Sequence-Specific Binary Fuzzy Complexes of Charged Intrinsically Disordered Proteins

Abstract

Intrinsically disordered proteins (IDPs) are important for biological functions. In contrast to folded proteins, molecular recognition among certain IDPs is "fuzzy" in that their binding and/or phase separation are stochastically governed by the interacting IDPs' amino acid sequences while their assembled conformations remain largely disordered. To help elucidate a basic aspect of this fascinating yet poorly understood phenomenon, the binding of a homo- or hetero-dimeric pair of polyampholytic IDPs is modeled statistical mechanically using cluster expansion. We find that the binding affinities of binary fuzzy complexes in the model correlate strongly with a newly derived simple "jSCD" parameter readily calculable from the pair of IDPs' sequence charge patterns. Predictions by our analytical theory are in essential agreement with coarse-grained explicit-chain simulations. This computationally efficient theoretical framework is expected to be broadly applicable to rationalizing and predicting sequence-specific IDP-IDP polyelectrostatic interactions.

51 pages, 11 figures. Accepted for Publication in J. Phys. Chem. B

References in corpus (13)

• Strong scaling of general-purpose molecular dynamics simulations on GPUs
• The Electrostatic Screening Length in Concentrated Electrolytes Increases with Concentration
• Phase separation and single-chain compactness of charged disordered proteins are strongly correlated
• Sequence-specific polyampholyte phase separation in membraneless organelles
• Model for disordered proteins with strongly sequence-dependent liquid phase behavior
• Phase Equilibria of Lattice Polymers from Histogram Reweighting Monte Carlo Simulations
• Random-phase-approximation theory for sequence-dependent, biologically functional liquid-liquid phase separation of intrinsically disordered proteins
• Charge Pattern Matching as a "Fuzzy" Mode of Molecular Recognition for the Functional Phase Separations of Intrinsically Disordered Proteins
• Coarse-Grained Residue-Based Models of Disordered Protein Condensates: Utility and Limitations of Simple Charge Pattern Parameters
• A Lattice Model of Charge-Pattern-Dependent Polyampholyte Phase Separation
• Theory of Polymer Chains in Poor Solvent: Single-Chain Structure, Solution Thermodynamics and Theta Point
• A unified analytical theory of heteropolymers for sequence-specific phase behaviors of polyelectrolytes and polyampholytes
• Polyelectrolytes in the presence of multivalent ions: gelation versus segregation

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• A Simple Explicit-Solvent Model of Polyampholyte Phase Behaviors and its Ramifications for Dielectric Effects in Biomolecular Condensates
• Subcompartmentalization of polyampholyte species in organelle-like condensates is promoted by charge pattern mismatch and strong excluded-volume interaction
• Assembly of Model Postsynaptic Densities Involves Interactions Auxiliary to Stoichiometric Binding
• Numerical Techniques for Applications of Analytical Theories to Sequence-Dependent Phase Separations of Intrinsically Disordered Proteins
• Small-Angle X-Ray Scattering Signatures of Conformational Heterogeneity and Homogeneity of Disordered Protein Ensembles
• Electrostatics of Salt-Dependent Reentrant Phase Behaviors Highlights Diverse Roles of ATP in Biomolecular Condensates
• Differential Effects of Sequence-Local versus Nonlocal Charge Patterns on Phase Separation and Conformational Dimensions of Polyampholytes as Model Intrinsically Disordered Proteins