Intrinsically disordered proteins (IDPs) are essential components for the formation of membraneless organelles, which play key functional and regulatory roles within biological systems. These complex assemblies form and dissolve spontaneously over time via liquid–liquid phase separation of IDPs. Mutations in their amino acid sequence can alter their phase behavior, which has been linked to the emergence of severe diseases. We study the conformation and phase behavior of a low-complexity domain of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) using coarse-grained implicit solvent molecular dynamics simulations. We systematically analyze how these properties are affected by the number of aromatic residues within the examined sequences. We find a significant compaction of the chains and an increase in the critical temperature with an increasing number of aromatic residues. The local persistence length is determined in single-chain simulations, revealing strong sequence-specific variations along the chain contour. Comparing single-chain and condensed-state simulations, we find many more collapsed polymer conformations in the dilute systems, even at temperatures near the estimated θ-temperature of the solution. These observations strongly support the hypothesis that aromatic residues play a dominant role in condensation, which is further corroborated by a detailed analysis of the intermolecular contacts, and conversely that important properties of condensates are captured in coarse-grained simulations. Interestingly, we observe density inhomogeneities within the condensates near criticality, which are driven by electrostatic interactions. Finally, we find that the relatively small fraction of hydrophobic residues in the IDPs results in interfacial tensions, which are significantly lower compared to typical combinations of immiscible simple liquids.
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21 October 2022
Research Article|
October 19 2022
Single-chain and condensed-state behavior of hnRNPA1 from molecular simulations
D. Janka Bauer
;
D. Janka Bauer
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Validation, Writing – original draft, Writing – review & editing)
1
Institute of Physics, Johannes Gutenberg University Mainz
, Staudingerweg 7, 55128 Mainz, Germany
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Lukas S. Stelzl
;
Lukas S. Stelzl
(Conceptualization, Methodology, Project administration, Supervision, Validation, Writing – original draft, Writing – review & editing)
1
Institute of Physics, Johannes Gutenberg University Mainz
, Staudingerweg 7, 55128 Mainz, Germany
2
Faculty of Biology, Johannes Gutenberg University Mainz
, 55128 Mainz, Germany
3
Institute of Molecular Biology (IMB)
, 55128 Mainz, Germany
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Arash Nikoubashman
Arash Nikoubashman
a)
(Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing)
1
Institute of Physics, Johannes Gutenberg University Mainz
, Staudingerweg 7, 55128 Mainz, Germany
a)Author to whom correspondence should be addressed: [email protected]
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a)Author to whom correspondence should be addressed: [email protected]
J. Chem. Phys. 157, 154903 (2022)
Article history
Received:
June 24 2022
Accepted:
September 13 2022
Citation
D. Janka Bauer, Lukas S. Stelzl, Arash Nikoubashman; Single-chain and condensed-state behavior of hnRNPA1 from molecular simulations. J. Chem. Phys. 21 October 2022; 157 (15): 154903. https://doi.org/10.1063/5.0105540
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