Scale‐free Spatio‐temporal Correlations in Conformational Fluctuations of Intrinsically Disordered Proteins

Abstract The self‐assembly of intrinsically disordered proteins (IDPs) into condensed phases and the formation of membrane‐less organelles (MLOs) can be considered as the phenomenon of collective behavior. The conformational dynamics of IDPs are essential for their interactions and the formation of a condensed phase. From a physical perspective, collective behavior and the emergence of phase are associated with long‐range correlations. Here the conformational dynamics of IDPs and the correlations therein are analyzed, using µs‐scale atomistic molecular dynamics (MD) simulations and single‐molecule Förster resonance energy transfer (smFRET) experiments. The existence of typical scale‐free spatio‐temporal correlations in IDP conformational fluctuations is demonstrated. Their conformational evolutions exhibit “1/f noise” power spectra and are accompanied by the appearance of residue domains following a power‐law size distribution. Additionally, the motions of residues present scale‐free behavioral correlation. These scale‐free correlations resemble those in physical systems near critical points, suggesting that IDPs are poised at a critical state. Therefore, IDPs can effectively respond to finite differences in sequence compositions and engender considerable structural heterogeneity which is beneficial for IDP interactions and phase formation.