The Small Molecule Interaction Database is a database containing protein domain-small molecule interactions. It uses a domain-based approach to identify domain families, found in the Conserved Domain Database (CDD), which interact with a query small molecule. The CDD from NCBI amalgamates data from several different sources; Protein FAMilies (PFAM), Simple Modular Architecture Research Tool (SMART), Cluster of Orthologous Genes (COGs), and NCBI's own curated sequences. The data in SMID is derived from the Protein Data Bank (PDB), a database of known protein crystal structures.
SMID can be queried by entering a protein GI, domain identifier, PDB ID or SMID ID. The results of a search provide small molecule, protein, and domain information for each interaction identified in the database. Interactions with non-biological contacts are normally screened out by default. 
SMID-BLAST is a tool developed to annotate known small-molecule binding sites as well as to predict binding sites in proteins whose crystal structures have not yet been determined. The prediction is based on extrapolation of known interactions, found in the PDB, to interactions between an uncrystallized protein with a small molecule of interest. SMID-BLAST was validated against a test set of known small molecule interactions from the PDB. It was shown to be an accurate predictor of protein-small molecule interactions; 60% of predicted interactions identically matched the PDB annotated binding site, and of these 73%  had greater than 80% of the binding residues of the protein correctly identified. Hogue, C et al. estimated that 45% of predictions that were not observed in the PDB data do in fact represent true positives.