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

TL;DR

This study compares how sequence-local and nonlocal charge patterns influence the conformational dimensions and phase separation of polyampholytes, revealing that nonlocality significantly affects chain size predictions, while both features similarly predict phase separation.

Contribution

It introduces a comparative analysis of charge pattern parameters, showing SCD's superiority in predicting chain dimensions and the comparable effectiveness of both parameters for phase separation.

Findings

SCD better predicts isolated-chain radii of gyration.

$ppa$ correlates more with condensed-phase interaction energy.

SCD accounts for nonlocal contact effects in chain dimensions.

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 ($R_{\rm g}$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 $R_{\rm g}$ 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.