Cavity-ligand binding in a simple two-dimensional water model

TL;DR

This study uses Monte Carlo simulations of a simple 2D water model to explore how hydrophobic ligands interact with surfaces of different curvatures, revealing dewetting and reorientation phenomena.

Contribution

It introduces a simple 2D water model to analyze hydrophobic ligand-surface interactions and hydration phenomena with curvature-dependent effects.

Findings

Dewetting occurs on hydrophobic surfaces, especially concave ones.

Water molecules reorient near hydrophobic surfaces.

Hydrogen bonding adapts to cavity formation and surface curvature.

Abstract

By means of Monte Carlo computer simulations in the isothermal-isobaric ensemble, we investigated the interaction of a hydrophobic ligand with the hydrophobic surfaces of various curvatures (planar, convex and concave). A simple two-dimensional model of water, hydrophobic ligand and surface was used. Hydration/dehidration phenomena concerning water molecules confined close to the molecular surface were investigated. A notable dewetting of the hydrophobic surfaces was observed together with the reorientation of the water molecules close to the surface. The hydrogen bonding network was formed to accommodate cavities next to the surfaces as well as beyond the first hydration shell. The effects were most strongly pronounced in the case of concave surfaces having large curvature. This simplified model can be further used to evaluate the thermodynamic fingerprint of the docking of hydrophobic ligands.