Dynamics and energetics of hydrophobically confined water

Abstract

The effects of water confined in regions between self-assembling entities is relevant to numerous contexts such as macromolecular association, protein folding, protein-ligand association, and nanomaterials self-assembly. Thus assessing the impact of confined water, and the ability of current modeling techniques to capture the salient features of confined water is important and timely. We present molecular dynamics simulation results investigating the effect of confined water on qualitative features of potentials of mean force describing the free energetics of self-assembly of large planar hydrophobic plates. We consider several common explicit water models including the TIP3P, TIP4P, SPC/E, TIP4P-FQ, and SWM4-NDP, the latter two being polarizable models. Examination of the free energies for filling and unfilling the volume confined between the two plates (both in the context of average number of confined water molecules and "depth" of occupancy) suggests TIP4P-FQ water molecules generally occupy the confined volume at separation distances larger than observed for other models under the same conditions. The connection between this tendency of TIP4P-FQ water and the lack of a pronounced barrier in the potential of mean force for plate-plate association in TIP4P-FQ water is explored by artificially, but systematically, populating the confined volume with TIP4P-FQ water at low plate-plate separation distances. When the critical separation distance [denoting the crossover from an unoccupied (dry) confined interior to a filled (wet) interior] for TIP4P-FQ is reduced by 0.5 Å using this approach, a barrier is observed; we rationalize this effect based on increased resistant forces introduced by confined water molecules at these low separations. We also consider the dynamics of water molecules in the confined region between the hydrophobes. We find that the TIP4P-FQ water model exhibits nonbulklike dynamics, with enhanced lateral diffusion relative to bulk. This is consistent with the reduced intermolecular water-water interaction indicated by a decreased molecular dipole moment in the interplate region. Analysis of velocity autocorrelation functions and associated power spectra indicate that the interplate region for TIP4P-FQ at a plate separation of 14.4 Å approaches characteristics of the pure water liquid-vapor interface. This is in stark contrast to the other water models (including the polarizable SWM4-NDP model).