Differential Effects of Sequence-Local versus Nonlocal Charge Patterns on Phase Separation and Conformational Dimensions of Polyampholytes as Model Intrinsically Disordered Proteins

Abstract

Conformational properties of intrinsically disordered proteins (IDPs) are governed by a sequence-ensemble relationship. To differentiate the impact of sequence-local versus sequence-nonlocal features of an IDP's charge pattern on its conformational dimensions and its phase-separation propensity, the charge "blockiness'' $\kappa$ and the nonlocality-weighted sequence charge decoration (SCD) parameters are compared for their correlations with isolated-chain radii of gyration ($R_{\mathrm{g}}$s) and upper critical solution temperatures (UCSTs) of polyampholytes modeled by random phase approximation, field-theoretic simulation, and coarse-grained molecular dynamics. SCD is superior to $\kappa$ in predicting $R_{\mathrm{g}}$ because SCD accounts for effects of contact order, i.e., nonlocality, on dimensions of isolated chains. In contrast, $\kappa$ and SCD are comparably good, though nonideal, predictors of UCST because frequencies of interchain contacts in the multiple-chain condensed phase are less sensitive to sequence positions than frequencies of intrachain contacts of an isolated chain, as reflected by $\kappa$ correlating better with condensed-phase interaction energy than SCD.

arXiv comment56 pages, 4 main-text figures, Supporting Information (containing supporting text, 1 supporting table, and 9 supporting figures), Table-of-Contents graphics, and 94 references. Accepted for publication The Journal of Physical Chemistry Letters

References in corpus (17)

• An efficient, multiple range random walk algorithm to calculate the density of states
• Comparative Roles of Charge, $\pi$ and Hydrophobic Interactions in Sequence-Dependent Phase Separation of Intrinsically Disordered Proteins
• Phase separation and single-chain compactness of charged disordered proteins are strongly correlated
• Sequence-specific polyampholyte phase separation in membraneless organelles
• Phase Equilibria of Lattice Polymers from Histogram Reweighting Monte Carlo Simulations
• Coarse-Grained Residue-Based Models of Disordered Protein Condensates: Utility and Limitations of Simple Charge Pattern Parameters
• Theory of Polymer Chains in Poor Solvent: Single-Chain Structure, Solution Thermodynamics and Theta Point
• A Modified Random Phase Approximation of Polyelectrolyte Solutions
• A unified analytical theory of heteropolymers for sequence-specific phase behaviors of polyelectrolytes and polyampholytes
• Analytical Formulation and Field-Theoretic Simulation of Sequence-Specific Phase Separation of Proteinlike Heteropolymers with Short- and Long-Spatial-Range Interactions
• Analytical Theory for Sequence-Specific Binary Fuzzy Complexes of Charged Intrinsically Disordered Proteins
• A Simple Explicit-Solvent Model of Polyampholyte Phase Behaviors and its Ramifications for Dielectric Effects in Biomolecular Condensates
• Theory and simulation of multiphase coexistence in biomolecular mixtures
• Subcompartmentalization of polyampholyte species in organelle-like condensates is promoted by charge pattern mismatch and strong excluded-volume interaction
• 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
• Heavy charged scalars from $c\bar{s}$ fusion: A generic search strategy applied to a 3HDM with $\mathrm{U}(1)\times \mathrm{U}(1)$ family symmetry

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