Pocket Crafter Workflow Overview. The Pocket Crafter workflow has been developed to construct de novo compounds in 3D by crafting atoms and bonds that precisely fit into specific tertiary protein pockets. Unlike methods dependent on reference ligands, our workflow enables thorough exploration of the desired pocket's characteristics. It virtually generates and selects hit compounds based on diverse SAR scaffolds, providing guidance to drug discovery projects not only for novel chemical synthesis but also for biological profiling of the interaction site. The overall Pocket Crafter workflow is depicted in Figure . It is a two-step scalable automated workflow suitable for GPU/CPU high-performance computing and cloud environments. The overall process is shown as following: tertiary protein pocket structure as the input; de novo binder generation with Pocket2Mol 3D generative chemistry approach; chemical-physical property filters; hit calling filters; SAR enrichment; the output of Pocket Crafter are novel diverse hit scaffolds with binding pose in tertiary protein pocket; interaction site profiling or de novo synthesis or archived library searching could be followed to generate a focused set of compounds for biological test.