Figures and data
Bibliographic values for different properties of phenylalanine and tyrosine.
(A) Solvation free energy (ΔGsolv) (Chang et al., 2007). (B) Probability distributions of min-maxed normalized hydropathy values λ from bibliographic hydrophobicity scales (Tesei et al., 2021). (C) Self-interaction energy (εii) from the Miyazawa-Jernigan contact matrix (Miyazawa and Jernigan, 1996). (D) Solubility in water at 25°C (Nozaki and Tanford, 1971).
(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) Representative simulation box with a fully solvated GSY condensate in slab geometry including a GGXGG peptide (spheres) and the capped amino acid mixture (G: white, S: yellow and Y: green). (B) Time series for the solvent accessible surface area (SASA) in a representative trajectory of the GGXGG peptide within the GSY condensate for different values of λ. (C) Time evolution of the density profiles calculated across the longest dimension of the simulation box (L) in the coexistence simulations. In blue we show the density in mg/mL of all the peptides, and in dark red that of the F/Y residue in the GGXGG peptide.
(A) Representative snapshots from the simulations of dense phases. G/S/F/Y dipeptides are shown as transparent surfaces (G: white, S: yellow, Y: green, F: purple). (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 (Calinsky and Levy, 2024). (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) Representative snapshots of REMD simulations of the GSY condensate at high (top) and low (bottom) temperatures. Colour code as in Figure 3. (B) Same for the GSF condensate. (C) Phase diagrams for GSY (green) and GSF (purple). Empty circles correspond to simulations and filled circles correspond to fitted critical temperatures (Tc) and densities (ρc).
(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) 
Copies of each of the terminally capped amino acid residues in the condensate simulations.
For GSY and GSF condensates, we use an equimolar mixture of all three components.
Number of molecules used in pure solvent simulations for the determination of dielectric constants.
Simulation times for each of the families of systems considered in this study.
For GSY and GSF condensates, we run triplicates. For the simulations in pure solvents (including water), a single simulation run was performed for each system.
Replicates of the GGXGG peptide simulations in the GSY condensate.
(A) Time series for the accessible surface area for different values of λ. (B) Density profiles of peptide (solid lines) and F/Y residue (right Y-axis) averaged over the simulation runs. (C) Time series for the density profiles of all peptides (blue) and the F2Y residue (red).
Work values for the forward and reverse alchemical transitions for different initial snapshots (bottom) and their distributions (top).
The BAR estimator is shown in the legend. Each panel corresponds to a different solvent. (A) TIP3P water. (B) Replicates of GSY condensates. (C) Replicates of GSF condensates.
Results for the GSY condensate in the TIP4P-Ew water model.
(A) Representative simulation box with a fully solvated GSY condensate in slab geometry including a GGXGG peptide (spheres) and the capped amino acid mixture (G: white, S: yellow and Y: green). (B) Time series for the solvent accessible surface area (SASA) for different values of λ. (C) Time evolution of the density profiles calculated across the longest dimension of the simulation box (L) in the coexistence simulations.
Results for the GSY condensate in the TIP4P-Ew water model.
Work values and their distribution for forward and backward transitions within water (A) and the GSY condensate (B).
Replicates of the GGXGG peptide simulations in the GSF condensate.
(A) Time series for the accessible surface area for different values of λ. (B) Density profiles of peptide (solid lines) and F/Y residue (right Y-axis) averaged over the simulation runs. (C) Time series for the density profiles of all peptides (blue) and the F2Y residue (red).
Density profiles at different temperatures for the GSY (A) and GSF (B) condensates.
Density profiles for sticker residues across the simulation box from the REMD simulations at room temperature.
Work values for the forward and reverse alchemical transitions for different initial snapshots (left) and their distributions (right).
The BAR estimator is shown in the legend. Each panel corresponds to a different solvent: (A) Acetone. (B) Benzene. (C) Cyclohexane. (D) Ethanol. (E) Hexanol. (F) Methanol. (G) Octanol. (H) Toluene.
