Inside Back Cover: Nucleation and Growth of Amino Acid and Peptide Supramolecular Polymers through Liquid–Liquid Phase Separation (Angew. Chem. Int. Ed. 50/2019)

2019 ◽  
Vol 58 (50) ◽  
pp. 18297-18297
Author(s):  
Chengqian Yuan ◽  
Aviad Levin ◽  
Wei Chen ◽  
Ruirui Xing ◽  
Qianli Zou ◽  
...  
Keyword(s):  
Phase Separation ◽  
Amino Acid ◽  
Liquid Phase ◽  
Nucleation And Growth ◽  
Liquid Phase Separation ◽  
Supramolecular Polymers ◽  
Back Cover ◽  
Liquid Liquid Phase Separation

Nucleation and Growth of Amino Acid and Peptide Supramolecular Polymers through Liquid–Liquid Phase Separation

2019 ◽  
Vol 131 (50) ◽  
pp. 18284-18291 ◽  
Author(s):  
Chengqian Yuan ◽  
Aviad Levin ◽  
Wei Chen ◽  
Ruirui Xing ◽  
Qianli Zou ◽  
...  
Keyword(s):  
Phase Separation ◽  
Amino Acid ◽  
Liquid Phase ◽  
Nucleation And Growth ◽  
Liquid Phase Separation ◽  
Supramolecular Polymers ◽  
Liquid Liquid Phase Separation

scholarly journals Targeted modulation of protein liquid-liquid phase separation by evolution of amino-acid sequence

2020 ◽  
Author(s):  
Simon M. Lichtinger ◽  
Adiran Garaizar ◽  
Rosana Collepardo-Guevara ◽  
Aleks Reinhardt
Keyword(s):  
Phase Separation ◽  
Amino Acid ◽  
Liquid Phase ◽  
Amino Acid Sequence ◽  
Amino Acid Sequences ◽  
Liquid Phase Separation ◽  
Computational Method ◽  
Coarse Grained ◽  
Intrinsically Disordered ◽  
Liquid Liquid Phase Separation

AbstractRationally and efficiently modifying the amino-acid sequence of proteins to control their ability to undergo liquid-liquid phase separation (LLPS) on demand is not only highly desirable, but can also help to elucidate which protein features are important for LLPS. Here, we propose an innovative computational method that couples a genetic algorithm to a sequence-dependent coarse-grained protein model to evolve the amino-acid sequences of phase-separating intrinsically disordered protein regions (IDRs), and purposely enhance or inhibit their capacity to phase-separate. We apply it to the phase-separating IDRs of three naturally occurring proteins, namely FUS, hnRNPA1 and LAF1, as prototypes of regions that exist in cells and undergo homotypic LLPS driven by different types of intermolecular interaction. We find that the evolution of amino-acid sequences towards enhanced LLPS is driven in these three cases, among other factors, by an increase in the average size of the amino acids. However, the direction of change in the molecular driving forces that enhance LLPS (such as hydrophobicity, aromaticity and charge) depends on the initial amino-acid sequence: the critical temperature can be enhanced by increasing the frequency of hydrophobic and aromatic residues, by changing the charge patterning, or by a combination of both. Finally, we show that the evolution of amino-acid sequences to modulate LLPS is strongly coupled to the composition of the medium (e.g. the presence or absence of RNA), which may have significant implications for our understanding of phase separation within the many-component mixtures of biological systems.

scholarly journals Solubility Parameters of Amino Acids on Liquid–Liquid Phase Separation and Aggregation of Proteins

2021 ◽  
Vol 9 ◽  
Author(s):  
Akira Nomoto ◽  
Suguru Nishinami ◽  
Kentaro Shiraki
Keyword(s):  
Amino Acids ◽  
Phase Separation ◽  
Amino Acid ◽  
Liquid Phase ◽  
Aromatic Amino Acids ◽  
Liquid Phase Separation ◽  
Solubility Parameters ◽  
Liquid Liquid Phase Separation

The solution properties of amino acids determine the folding, aggregation, and liquid–liquid phase separation (LLPS) behaviors of proteins. Various indices of amino acids, such as solubility, hydropathy, and conformational parameter, describe the behaviors of protein folding and solubility both in vitro and in vivo. However, understanding the propensity of LLPS and aggregation is difficult due to the multiple interactions among different amino acids. Here, the solubilities of aromatic amino acids (SAs) were investigated in solution containing 20 types of amino acids as amino acid solvents. The parameters of SAs in amino acid solvents (PSASs) were varied and dependent on the type of the solvent. Specifically, Tyr and Trp had the highest positive values while Glu and Asp had the lowest. The PSAS values represent soluble and insoluble interactions, which collectively are the driving force underlying the formation of droplets and aggregates. Interestingly, the PSAS of a soluble solvent reflected the affinity between amino acids and aromatic rings, while that of an insoluble solvent reflected the affinity between amino acids and water. These findings suggest that the PSAS can distinguish amino acids that contribute to droplet and aggregate formation, and provide a deeper understanding of LLPS and aggregation of proteins.

scholarly journals Targeted modulation of protein liquid–liquid phase separation by evolution of amino-acid sequence

2021 ◽  
Vol 17 (8) ◽  
pp. e1009328
Author(s):  
Simon M. Lichtinger ◽  
Adiran Garaizar ◽  
Rosana Collepardo-Guevara ◽  
Aleks Reinhardt
Keyword(s):  
Phase Separation ◽  
Amino Acid ◽  
Liquid Phase ◽  
Amino Acid Sequence ◽  
Amino Acid Sequences ◽  
Liquid Phase Separation ◽  
Computational Method ◽  
Coarse Grained ◽  
Intrinsically Disordered ◽  
Liquid Liquid Phase Separation

Rationally and efficiently modifying the amino-acid sequence of proteins to control their ability to undergo liquid–liquid phase separation (LLPS) on demand is not only highly desirable, but can also help to elucidate which protein features are important for LLPS. Here, we propose a computational method that couples a genetic algorithm to a sequence-dependent coarse-grained protein model to evolve the amino-acid sequences of phase-separating intrinsically disordered protein regions (IDRs), and purposely enhance or inhibit their capacity to phase-separate. We validate the predicted critical solution temperatures of the mutated sequences with ABSINTH, a more accurate all-atom model. We apply the algorithm to the phase-separating IDRs of three naturally occurring proteins, namely FUS, hnRNPA1 and LAF1, as prototypes of regions that exist in cells and undergo homotypic LLPS driven by different types of intermolecular interaction, and we find that the evolution of amino-acid sequences towards enhanced LLPS is driven in these three cases, among other factors, by an increase in the average size of the amino acids. However, the direction of change in the molecular driving forces that enhance LLPS (such as hydrophobicity, aromaticity and charge) depends on the initial amino-acid sequence. Finally, we show that the evolution of amino-acid sequences to modulate LLPS is strongly coupled to the make-up of the medium (e.g. the presence or absence of RNA), which may have significant implications for our understanding of phase separation within the many-component mixtures of biological systems.

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