When setting up a molecular simulation, a solute is rarely simulated in isolation. Most realistic chemical or biochemical processes occur in condensed-phase environments, typically involving explicit solvent molecules. This entails first, specifying the boundaries (often periodic) within which the simulation will run, ensuring that the box dimensions are sufficient to avoid unphysical interactions caused by boundary effects. Second, surrounding the solute with a sufficient buffer of solvent molecules, typically ensuring the system density matches experimental conditions or is otherwise physically reasonable .