The conditions for chemical protein-protein cross-linking using the reagents pimelic dihydrazide (PDH) and 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) chloride were optimized using a set of five model proteins and two large complexes, the 20S proteasome and the 70S ribosome. This dataset contains data from the model proteins only.