The complexity of the system and the relevant questions one can answer, can vary significantly. "Easy" systems, such as a monomeric protein without cofactors, can involve around 30,000 atoms and are relatively straightforward to simulate (Fig. ). "Medium" systems, such as a proteinligand complex (Fig. ) may contain about 100,000 atoms, requiring more computational effort and resources, as well as careful consideration of small-molecule force field as well as the initial pose of the protein-ligand complex. Lastly, the most biologically relevant but "hard" systems, such as membrane proteins embedded in lipid bilayers, can exceed 300,000 atoms. These larger and more complex systems demand significantly more computational power and time to simulate due to the increased time per integration step (Fig. ). If one has access to specialized HPC hardware, it may also become feasible to simulate much larger "ultrahard" systems that would not be possible using standard commodity computing hardware; this includes being able to simulate larger systems like virions, aerosolized particles, and higher-order systems in atomic detail . Since such systems remain out of reach to run on standard Chapter simulation hardware in parallel, we will not be discussing them here.