Supplementary results for the Nature paper entitled “Observation of a Drying Tranition in the Collapse of the Melittin Tetramer” by P. Liu, Xuhui Huang, Ruhong Zhou and B. J. Berne.
Supplementary Figure 1:
Figure S1: More trajectories for the number of water molecules inside the channel of melittin tetramer versus the MD simulation time. The separation between the two dimers is 5.5 Å (D=5.5 Å). The heavy atoms of protein are constrained by a harmonic potential. Only water molecules near the center of the channel are counted, the center of the channel being definedas the region with a spherical radius of 10 Å from the center of the tetramer. Different curves shown in the graph correspond to simulations with different starting configurations (same protein conformer solvated in different water boxes). The initial water diffusive motion before the drying transition can take up to 400-500ps; however, once the cooperative transition happens, it is very fast and can take as little as 100ps.
Supplementary Figure 2:
(a) (b) (c)
Figure S2: More trajectories for the number of water molecules inside the channel of mutated melittin tetramers with D =5.5 Å as a function of MD simulation time. (a) The residue ILE2 is mutated to ALA. No dramatic drying is observed in all the trajectories. (b) The residue ILE17 is mutated to ALA. The drying transition is observed in all the trajectories. In some cases, it takes as fast as 200ps for the drying transition to happen, but in some other cases, the drying transition happens after 600ps. (c) The residue ILE20 is mutated to ALA. The drying transition is observed in all the trajectories. In all cases, it takes more than 400ps for the drying transition to occur.The heavy atoms of the protein are constrained by a harmonic potential. Different curves in the same graph correspond to simulations with different starting configurations
Supplementary Figure 3:
(a)
(b)
Figure S3: The number of water molecules in the melittin tetramer channel as a function of dimer-dimer separation distance during the collapse of the tetramer. (a) The initial dimer-dimer distance D=6 Å. (b) The initial dimer-dimer distance D=5.5 Å. These graphs indicate that in most cases the drying transition is coincidental with the hydrophobic collapse; however, there is also evidence (e.g. Fig. 3(a), right graph) showing that drying can happen before the hydrophobic collapse, i.e. there is a drying induced collapse.
Supplementary Note:
A final point, we also simulated the tetramer in the ``crystal environment'' to verify the stability of the protein in the current force field, by using the measured crystal lattice, a=60.832, b=38.293, and c=42.211, in defining the water box with periodic boundary condition. We found that the native structure is very stable, with an all heavy-atom RMSD less than 2.0, during the 5ns NPT simulation. The tetramers from various single mutations, total nine (each of the 3 ILE residues mutated to VAL, ALA, and GLY, respectively) are found to be stable too. More interestingly, it was found that there exist 3-4 water molecules inside the native tetramer cavity during the MD simulation, which agrees very well with the experimental findings.