Many intrinsically disordered proteins (IDPs) , proteinsthat do not fold into a unique tertiary structure in isolation because of their depletion in hydrophobicity whereas enrichment in charge and aromaticity, retain their structural disorderness when participating in IDP-IDP binding andIDP phase separation via a sequence-specific "fuzzy  " molecular recognition mechanism. We implement the cluster expansion method in statistical mechanics to develop an analytical theory for elucidating the nature of the fuzzy Coulomb interaction between two charged IDPs . We apply the theory to calculate binding affinities between various pairs of IDP sequences, and extract a parameter jSCDencompassing the sequence-specific IDP-IDP interaction. Our theory provides a general framework to investigate IDP-IDP interaction .
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 .
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Many intrinsically
Intrinsically
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, proteinsthat do not fold into a unique tertiary structure in isolation because of their depletion in hydrophobicity whereas enrichment in charge and aromaticity, retain their structural disorderness when participating in IDP-IDP binding andIDP phase separation via a sequence-specific
are important for biological functions. In contrast to folded proteins, molecular recognition among certain IDPs is
A
" 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
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molecular recognition mechanism. We implement the cluster expansion method in statistical mechanics to develop an analytical theory for elucidating the nature of the fuzzy Coulomb interaction between two charged IDPs . We apply the theory to calculate binding affinities between various pairs of IDP sequences, and extract a parameter jSCDencompassing the
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
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interaction. Our theory provides a general framework to investigate IDP-IDP interaction
polyelectrostatic interactions