Water properties inside nanoscopic hydrophobic pocket studied by computer simulations

Area of Science:

• Computational chemistry
• Physical chemistry
• Biophysics

Background:

• Understanding water behavior near hydrophobic surfaces is crucial for molecular recognition and drug design.
• Hydrophobic pockets in biological systems influence binding affinities and reaction rates.
• Previous studies often focused on flat hydrophobic surfaces, limiting insights into curved interfaces.

Purpose of the Study:

• To investigate the structure and dynamics of water within an 8 Å radius hemispherical hydrophobic pocket.
• To analyze water density, hydrogen bonding, and residence times spatially.
• To explore the influence of surface curvature on water behavior and pocket occupancy.

Main Methods:

• Molecular dynamics (MD) simulations in the NVT ensemble.
• Projection of water properties onto two-dimensional planes for spatial analysis.
• Analysis of pocket occupancy, density, hydrogen bonding, and residence times.

Main Results:

• Significantly depleted water density within the hydrophobic pocket compared to bulk water.
• Fluctuations between empty and bulk-like fluid states in the pocket, driven by collective water behavior.
• Small free energy differences suggest the pocket radius is near a critical transition point for water phases.

Conclusions:

• Surface curvature significantly alters water behavior near hydrophobic pockets compared to flat surfaces.
• The observed water dynamics and pocket occupancy provide insights into binding site desolvation.
• These findings aid in predicting binding energies more accurately in biological systems.