During ligand preparation, computational chemists assign partial charges to each ligand atom. These atomic partial charges aim to model a given molecule's electrostatic interactions with its environment, and are particularly crucial for strong polar and hydrogen bonding interactions often present in binding sites. Thus, partial charges have a major impact on downstream calculated values such as free energy estimates. The nature of electrons and their densities makes them di cult to model, especially as static floating point values. While polarizable force fields are available and go beyond fixed atom-centered partial charges, the classical fixed-charge model is still the most common model for free energy calculations. In fixed-charged models, atomic partial charges are modeled by static floating point values. It is important to note, however, that partial charges are not a physical observable, meaning that no single set of partial charges is "best". Rather, researchers typically assign static partial charges that attempt to replicate the electrostatic field or potential around the molecule that would be derived from suitable quantum chemical calculations.