Analytical Theory for Sequence-Specific Binary Fuzzy Complexes of Charged Intrinsically Disordered Proteins
arXiv:1910.11194 · doi:10.1021/acs.jpcb.0c04575
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