Updated project metadata. This submission includes the raw data analyzed and search results described in our manuscript “Proteome-Scale Recombinant Standards And A Robust High-Speed Search Engine To Advance Cross-Linking MS-Based Interactomics”. In this study, we develop a strategy to generate a well-controlled XL-MS standard by systematically mixing and cross-linking recombinant proteins. The standard can be split into independent datasets, each of which has the MS2-level complexity of a typical proteome-wide XL-MS experiment. The raw datasets included in this submission were used to (1) guide the development of Scout, a machine learning-based search engine for XL-MS with MS-cleavable cross-linkers (batch 1), test different LC-MS acquisition methods (batch 2), and directly compare Scout to widely used XL-MS search engines (batches 3 and 4).