Sensitivity of Protein Glass Transition to the Choice of Water Model.

The sensitivity of protein glass transition temperature and dynamics of Trp-cage miniprotein to the choice of water models have been investigated by performing molecular dynamics simulations at different temperatures between 130 and 300 K using mTIP3P, TIP4P, and TIP4P-Ew water models with the CHARMM22 force field. Analysis of the structure of the protein and the ordering of the hydration shell water molecules revealed correlated dynamic crossovers of the protein and its hydration water. It is demonstrated that the parametrization of different water models is robust enough to probe the onset temperatures for the two dynamic crossovers of the peptide: the first one around 150 K which is attributed to active methyl group rotations and the second one around 200-230 K specifically pertaining to glass transition of the protein. The behavior of the protein has been found to be qualitatively similar to the three water models employed, while the structural ordering and number of hydration shell waters vary significantly among the 3-site and 4-site water models. The changes in the probability density map of methyl hydrogens of the protein with temperature also show sensitivity to the choice of water model.