Optimal geometries for each monomer were generated using CREST 2 v. 2.12. These monomers were then manually placed near each other to create initial guess geometries for each complex. For the complexes from the S30-L dataset, the initial guess geometries were intentionally dissimilar to the published dimer geometries, as a test of whether the published geometries could be reliably regenerated. These initial guess geometries were then used as input for each method tested. All initial guess geometries are available in the SI. Computations were performed using GBSA to simulate solvent. Complexes containing asphaltene model compounds (monomers 1, 2a, 2b, 4 through 8, 13, 14, and 25) were computed using simulated benzene solvent. Complexes containing peptides (monomers 9 through 12, 23, and 24) were computed using simulated water solvent. Complexes from the S30-L test set were computed using the solvents stipulated by the S30-L test set. That is, complex 15-16 was computed in simulated dichloromethane, complex 17-18 was computed in simulated chloroform, complex 19-20 was computed in simulated carbon disulfide, and complex 21-22 was computed in simulated water. The cluster of ten water molecules was computed in vacuum. For single molecules 23 and 24, the length of the N-H and O-H bonds had to be constrained to prevent chemical reactions during the metadynamics cycles.