## Lab software

The Solvaware package is a workflow that runs and analyses molecular dynamics (MD) trajectories to estimate hydration free energies by computing the contribution of different subvolumes around a solute. The accurate calculation of hydration free energies is a vital goal in computational modelling of biological and engineered aqueous systems.

Water is the most important molecule in biology, as the interaction between biomolecules must compete with the interactions of the individual molecules with water. Thus water is directly involved in every single intermolecular interaction in an aqueous environment. Unfortunately, the complexity of intermolecular interactions and the vast number of degrees of freedom in even the simplest systems commonly confound computational approaches.

In particular, the calculation of entropy remains a challenging and computationally demanding problem. Solvaware applies the statistical mechanical method of inhomogeneous fluid solvation theory (IFST) to determine the enthalpy and entropy of solvation.

IFST can be used to analyse MD simulations in explicit solvent and derive the contribution of specific spatial subvolumes to the solvation free energy. IFST is unique in combining the accuracy of a rigorous treatment of explicit water with the spatial decomposition of the results, which leads to understanding and drives the generation of ideas.

In addition, useful predictions can be derived from a single simulation. IFST analysis is performed by calculating the mean enthalpy and entropy in different subvolumes using snapshots from the MD trajectory.

Solvaware is available through the ARCHER website.

**Legend** – Contour plot of the relative free energy density (summed enthalpy and entropy) for hydration of the cucurbit[7]uril system.