Small molecule-binding [sm] refers to proteins that interact with small molecules either catalytically or non-catalytically. Here, "small molecules" means all types of substrates except metal ions and macromolecules (that is, DNA, RNA, protein, or oligosaccharide carbohydrates). HotPatch's statistical parameters for small molecule-binding are derived by training on a set of structures in this class.

In training on their known functional sites, the sites were defined by:

• Annotations as functional residues (involved in catalysis, substrate recognition, binding etc.) in the SFR Database, which were mostly obtained from the literarture.
• Proximity of 4Å to a small molecule (if present in the structure), or to a known surrogate of the normal molecule (e.g. phosphate ions known to bind where ATP normally does).

Size of training set: 246 structures (229 with hydrogens added, for electrostatics & neural networks).