# System size dependence of hydration shell occupancy

## TL;DR

This paper investigates how the size of the system influences the free energies associated with hydration shells, revealing that both hydrophilic and hydrophobic effects vary with system size, impacting macromolecular hydration understanding.

## Contribution

It demonstrates the system size dependence of hydration free energies and clarifies the balance of hydrophilic and hydrophobic contributions within the quasichemical framework.

## Key findings

- Hydration shell evacuation free energies depend on system size.
- Hydrophilic and hydrophobic contributions decrease as system size increases.
- Large systems are necessary for accurate macromolecular hydration modeling.

## Abstract

The free energies to evacuate the first hydration shell around a solute and a cavity defined by the first hydration shell depend on the system size. This observation interpreted within the quasichemical theory shows that both the hydrophilic and the hydrophobic contributions to hydration depend on the system size, decreasing with increasing system size. Although the net hydration free energy benefits somewhat from the balancing of hydrophilic and hydrophobic contributions, a large system still appears necessary to describe the effect of the solvent on the macromolecule.