Results discussed in previous sections showed a roughly two-fold increase in sampling efficiency using the TIP3P-F water model for small peptide and ribonucleotide systems. To test if similar effects can be expected in simulations of properly folded proteins, we selected ubiquitin 40 as a model system. In total, ten independent molecular dynamics simulations of ubiquitin with a length of 2.7 µs per replica were used to calculate statistics and for error analysis. First, time series of the radius of gyration, R g , were generated to calculate their distribution and expectation value. Panel D of Figure compares the numerical cumulative distribution functions observed in simulations with TIP3P and TIP3P-F. The empirical distributions and the averages in Table indicate that simulations with both water models lead to essentially the same results. Additionally, the panel E in Figure shows a substantial decrease in the decorrelation rate of this variable when using the TIP3P-F water model, particularly in the short and mid-time scale. The amount of acceleration can be appreciated quantitatively by comparing the integrated autocorrelation times of both systems in Table and it is also consistent with previous results. On the other hand, the exponential characteristic time of the slowest apparent process is not clearly different between the two water models. The associated motions may thus be dominated by "internal friction". However, the signal-to-noise ratio in the points used for the linear fit is low, making differences in the slope difficult to detect, and the respective time scale approaches the overall duration of the simulations. In addition to the R g time series, the collective dynamics of the α-carbon backbone atoms was analyzed. First, an average protein structure in TIP3P and TIP3P-F water was calculated by repeatedly aligning and averaging all structures from the respective molecular dynamics runs until convergence was achieved. Panel A of Figure shows a superposition of the average structures from trajectories using the two water models, demonstrating that average backbone conformation is independent of water mass. Afterwards, the root-meansquare fluctuation (RMSF) values of every α carbon atom about their average position was generated and a cutoff of 0.1 nm was applied to select a rigid skeleton for the generation of the time series, as shown in panel B of Figure . Then, the trajectories were re-aligned with respect to this ubiquitin core. Time series of the RMSD of the α carbon atoms from the core average were generated. The autocorrelation functions of the time series are depicted in panel C of Figure and the integrated and exponential autocorrelation times are reported in Table . According to the results, the TIP3P-F water model reduces the decorrelation times by about 30% to 40% with respect to the standard TIP3P model. Therefore, the TIP3P-F model speeds up the dynamics also for a folded protein. However, the slowest motions captured in the autocorrelation functions appear to decay with similar characteristic times τ exp for TIP3P and TIP3P-F, indicating that the underlying processes are dominated by internal friction. shows that the area per lipid values are also identical across the two water models. However, due to the reduced viscosity of the surrounding aqueous medium, the diffusion coefficient of the lipids is increased by ∼ 25%.