Competition of hydrophobic and Coulombic interactions between nano-sized solutes

TL;DR

This study investigates how hydrophobic and Coulombic interactions influence the forces between nano-sized charged solutes in water, revealing complex behaviors depending on charge patterns and emphasizing the importance of detailed modeling for protein aggregation.

Contribution

It provides new insights into the interplay of hydrophobic and electrostatic forces on nanometer-scale solutes with various charge distributions, highlighting the significance of explicit solvent and detailed charge modeling.

Findings

Hydrophobic attraction arises from solvent depletion between neutral solutes.

High charge reduces hydrophobic attraction, leading to repulsion.

Discrete charge patterns induce reentrant attraction due to patch effects.

Abstract

The solvation of charged, nanometer-sized spherical solutes in water, and the effective, solvent-induced force between two such solutes are investigated by constant temperature and pressure Molecular Dynamics simulations of model solutes carrying various charge patterns. The results for neutral solutes agree well with earlier findings, and with predictions of simple macroscopic considerations: substantial hydrophobic attraction may be traced back to strong depletion (``drying'') of the solvent between the solutes. This hydrophobic attraction is strongly reduced when the solutes are uniformly charged, and the total force becomes repulsive at sufficiently high charge; there is a significant asymmetry between anionic and cationic solute pairs, the latter experiencing a lesser hydrophobic attraction. The situation becomes more complex when the solutes carry discrete (rather than uniform) charge patterns. Due to antagonistic effects of the resulting hydrophilic and hydrophobic ``patches'' on the solvent molecules, water is once more significantly depleted around the solutes, and the effective interaction reverts to being mainly attractive, despite the direct electrostatic repulsion between solutes. Examination of a highly coarse-grained configurational probability density shows that the relative orientation of the two solutes is very different in explicit solvent, compared to the prediction of the crude implicit solvent representation. The present study strongly suggests that a realistic modeling of the charge distribution on the surface of globular proteins, as well as the molecular treatment of water are essential prerequisites for any reliable study of protein aggregation.