Conventional molecular dynamics simulations on 50 ns to 1 μs time scales were used
to study the effects of explicit solvent models on the conformational behavior and
solvation of two oligopeptide solutes: α-helical EK-peptide (14 amino acids) and a
β-hairpin chignolin (10 amino acids). The widely used AMBER force fields (ff99, ff99SB,
and ff03) were combined with four of the most commonly used explicit solvent models
(TIP3P, TIP4P, TIP5P, and SPC/E). Significant differences in the specific solvation
of chignolin among the studied water models were identified. Chignolin was highly
solvated in TIP5P, whereas reduced specific solvation was found in the TIP4P, SPC/E,
and TIP3P models for kinetic, thermodynamic, and both kinetic and thermodynamic reasons,
respectively. The differences in specific solvation did not influence the dynamics
of structured parts of the folded peptide. However, substantial differences between
TIP5P and the other models were observed in the dynamics of unfolded chignolin, stability
of salt bridges, and specific solvation of the backbone carbonyls of EK-peptide. Thus,
we conclude that the choice of water model may affect the dynamics of flexible parts
of proteins that are solvent-exposed. On the other hand, all water models should perform
similarly for well-structured folded protein regions. The merits of the TIP3P model
include its high and overestimated mobility, which accelerates simulation processes
and thus effectively increases sampling.