Proteins containing prion-like low complexity domains (PLDs) are common drivers of the formation of biomolecular condensates and are prone to misregulation due to amino acid mutations. Here, we exploit the accuracy of our residue-resolution coarse-grained model, Mpipi, to quantify the impact of amino acid mutations on the stability of 140 PLD mutants from six proteins (hnRNPA1, TDP43, FUS, EWSR1, RBM14, and TIA1). Our simulations reveal the existence of scaling laws that quantify the range of change in the critical solution temperature of PLDs as a function of the number and type of amino acid sequence mutations. These rules are consistent with the physicochemical properties of the mutations and extend across the entire family tested, suggesting that scaling laws can be used as tools to predict changes in the stability of PLD condensates. Our work offers a quantitative lens into how the emergent behavior of PLD solutions vary in response to physicochemical changes of single PLD molecules.
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| http://dx.doi.org/10.7554/eLife.99068 | DOI Listing |
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