The parameterization process is dependent on the system size and somewhat dependent on monomer type. Figure shows a clear correlation between the time to parameterize and the number of atoms in the system, with protein systems also uniformly taking more time to parameterize than large homopolymer systems. The Open Force Field toolkit implements the SMIRNOFF parameterization process with substructure query matching, which involves solving the subgraph isomorphism problem for a chemical topology. Subgraph ismorphism is an NP-complete problem and scales exponentially with the size of the graph and subgraph, as seens in Figure . The small reduction in parameterization time with large homopolymers as compared to large proteins is explained by the construction of the homopolymers, which contained on average more individual chains than the protein systems for the same total number of atoms. Proteins typically include between 1-4 chains/domains, whereas the homopolymer systems contained multiple 1000-atom chains (for example, polymethylmethacrylate contained 81 chains). In testing, increasing the number of polymer chains at a fixed total system size was found to reduce the parameterization time of the electrostatics for increasingly large systems due to the pre-existing OpenFF parameterization software.