Peptide diffusion in biomolecular condensates

Abstract

Diffusion determines the turnover of biomolecules in liquid-liquid phase-separated condensates. We considered the mean square displacement and thus the diffusion constant for simple model systems of peptides GGGGG, GGQGG, and GGVGG in aqueous solutions after phase separation by simulating atomic-level models. These solutions readily separate into aqueous and peptide-rich droplet phases. We noted the effect of the peptides being in a solvated, surface, or droplet state on the peptide's diffusion coefficients. Both sequence and peptide conformational distribution were found to influence diffusion and condensate turnover in these systems, with sequence dominating the magnitude of the differences. We found that the most compact structures for each sequence diffused the fastest in the peptide-rich condensate phase. This model result may have implications for turnover dynamics in signaling systems.

Figure 1

Snapshots of the three MD simulations taken after $400$ ns total simulation time. (A), (B), and (C) correspond to the GGGGG, GGQGG, and GGVGG systems, respectively. Liquid droplet states are colored red, while solvated peptide monomers are blue and nondroplet peptide clusters in solution are colored green. Water is not shown for graphical clarity. To see this figure in color, go online.

Figure 2

Comparison of the diffusion coefficients for GGGGG, GGQGG, and GGVGG peptides in the solvated, surface, and liquid droplet phases. Error bars represent standard error of the mean.

Figure 3

Diffusion coefficient versus $R_{\text{gyr}}$ windows for GGGGG, GGQGG, and GGVGG. See the legend within the figure for bin definitions. $R_{\text{gyr}}$ was calculated using only α carbons.