Bibliographic values for different properties of phenylalanine and tyrosine. (A) Solvation free energy (∆Gsolv).28 (B) Probability distributions of min-maxed normalized hydropathy values λ from bibliographic hydrophobicity scales.20 (C) Self-interaction energy (εii) from the Miyazawa-Jernigan contact matrix. 29 (D) Solubility in water at 25°C.33

(a) Thermodynamic cycle used in this study for the estimation of free energy differences upon mutation for the insertion of a peptide in a molecular condensate. (B) Schematic of the process of contact formation between two molecules i and j used in the quantum chemical calculations. We consider that contact formation involves the transfer from water (blue) to a different medium (orange) and the interaction in this medium between the entities involved.

(A) Time series for the accessible surface area of the GGXGG in the GSY condensate for different values of λ. (B) Time series for the density profiles of all peptides (blue) and the GGXGG peptide (red) in the coexistence simulations. (C) Representative simulation box with a fully solvated condensate in slab geometry including a GGXGG peptide (spheres) and the capped amino acid mixture (G: white, S: yellow and Y: green).

(A) Representative snapshots from the simulations of dense phases. (B) Interaction matrix for the normalized number of contacts between different pairs of amino acid residues in the condensates (top) and for each type of amino acid (bottom). (C) Density plots for side chain interactions between aromatic side chains, as characterised by the mean inter-residue distance and the angle θ between the vectors normal to the rings.72 (D) Density plots for sp2-π interactions between amide bonds and aromatic side chains, as characterised by the mean inter-group distance and the angle θ between the vectors normal to the peptide bond and ring planes. In all panels, results for GSY and GSF condensates are shown on the top and bottom, respectively. Representative snapshots of relevant interactions for each type of pair are shown.

(A) Radial distribution function for water oxygen around the Cζ in Phe/Tyr for GSF and GSY condensates. We show a representative overlay of simulation snapshots where water molecules are hydrogen-bonded to the Tyr side chain. (B) Transfer free energy differences from water to a different medium between Tyr and Phe. We consider condensates (green), polar solvents (orange) and apolar solvents (blue). (C) Same as a function of calculated dielectric constant, ε.

(A) and (B) for different interaction pairs ij and different solvents as a function of the dielectric constant, ε. (C) Optimized geometries from quantum chemical calculations for Phe and Tyr interaction pairs. (D) with respect to the cross-F-F interaction for different solvents as a function of the dielectric. Different symbols correspond to the different solvent types. Filled: alcohols; empty: alkanes/benzenes; lines: water with different dielectric.