Fig. 2. MD simulations predict that the intrinsically disordered region (IDR) in the juxtamembrane linker of syt1 mediates liquid-liquid phase separation (LLPS).

a Analysis using the VL-XT algorithm and PONDR software reveals that the segment comprising of residues 83–133 in the juxtamembrane linker of syt1 has a high probability (>0.5) of being disordered. b Left: MD simulation of droplet formation and stabilization by the isolated syt1 (80–142) juxtamembrane linker. Right: The droplet remains intact after 5 µs of simulation. All molecules stay in the dense phase with little branching in the system. c Left: Same as b Left but for the isolated syt1 (80 JuxtaK-142) mutant linker. Right: The droplet does not retain its shape and dissolves within 5 μs of the simulation protocol. Scale bars, 4 nm. (See Supplementary Movies 1, 2 for the movies). d Distribution of the gain/loss in the number of contacts (ΔQ) between copies of either the WT or JuxtaK mutant linker. The lysine substitutions shifted the distribution to the left, indicating a loss in the number of pairwise contacts compared to the same number of isolated chains. In panels b and c, the color code for the amino acid residues is as follows: blue, positive charge; red, negative charge; yellow, non-polar; green, polar. An explicit solvent coarse-grained molecular dynamics simulation with a reparametrized MARTINI v3.0 force field was used in this analysis. The ionic strength of the buffer was 100 mM NaCl. Each MD simulation is a result of n = 2 trajectories. Source data are provided as a Source Data file.