Local order, energy, and mobility of water molecules in the hydration shell of small peptides.

The extent to which the presence of a biomolecular solute modifies the local energetics of water molecules, as measured by the tagged molecule potential energy (TPE), is examined using molecular dynamics simulations of the beta-hairpin of 2GB1 and the alpha-helix of deca-alanine in water. The CHARMM22 force field, in conjunction with the TIP3P solvent water model, is used for the peptides, with simulations of TIP3P and SPC/E water used as benchmarks for the behavior of bulk solvent. TIP3P water is shown to have significantly lower local tetrahedral order and higher binding energy than SPC/E at the same state point. The TIP3P and SPC/E water models show very similar dynamical correlations in the TPE fluctuations on frequency scales greater than 0.1 cm(-1). In addition, the two models show the same linear correlation between mean tetrahedral order and binding energy, suggesting that the relationship between choice of water models and simulated hydration behavior may involve a complex interplay of static and dynamic factors. The introduction of a peptide in water modifies the local TPE of water molecules as a function of distance from the biomolecular interface. There is an oscillatory variation in the TPE with distance from the peptide for water molecules lying outside a 3 A radius and extending to at least 10 A. These variations are of the order of 2-5% of the bulk TPE value and are anticorrelated with variations in local tetrahedral order in terms of locations of maxima and minima, which may be understood in terms of the relative contribution of van der Waals and Coulombic contributions to the TPE. The distance-dependent variations in local order and energetics are essentially the same for the beta-hairpin of 2GB1 as well as deca-alanine. Within a radius of 3 A, the perturbation of the solvent structure is very significant with local TPEs that are 10-15% lower than the bulk value. The chemical identity of side-chain residues and the secondary structure play an important role in determining residue-dependent variations in the TPEs. The variation in the residue-dependent tagged molecule potential energies is of the order of 3-5%, while the local residence times vary by a factor of approximately 5. The correlation of the local residence times with the local energetics within the innermost hydration layer is weak, though charged residues typically have low binding energies and large residence times.