CACHE will present and organize a variety of "hit-finding" challenges to the community. As a part of this, and as described in detail below, CACHE will identify suitable protein targets, curate the virtual chemical libraries, define success parameters for predictions, and solicit predictions for hit compounds. For evaluation, CACHE will purchase or otherwise procure the predicted compounds, experimentally measure the binding of the compounds to their intended target, calculate other key properties of the active compounds, and share the outcomes openly with the community (FIG. ). We envision that CACHE, like CASP, will organize multiple rounds of challenges, providing on-going opportunities for algorithm developers to improve and test their methods. challenges to the community, including assessment criteria. 2. Virtual libraries: CACHE will establish and host two virtual libraries; a make-on-demand library (REAL, ZINC20) and a library comprising compounds synthetically accessible by chemists in academia or industry (bespoke chemistry). 3. Participants predict chemical matter & CACHE experimentally tests compounds: Each participant will have opportunity to make two cycles of predictions per round. CACHE will procure and assay the predicted compounds. At this stage, structures of compounds will be made available to all participants, but screening data will be provided only to the specific participant and competition management, in order to serve as a starting point for an additional cycle of predictions. 4. Compounds, data placed in the public domain: Once the second cycle is complete, the data package, including all structures and screening data, as well as an assessment of each compound, will be made available to all, without restriction.