The SMARTS line notation is expressive and allows extremely precise and transparent substructural specification and atom typing.
Additional SMARTS development was made at Daylight Chemical Information Systems, Inc, which is a private company that was spun out of the software side of MedChem.
The SSSR model has been criticised by OpenEye[5] who, in their implementation of SMARTS, use R to denote the number of ring bonds for an atom.
For example, the more reactive (with respect to electrophilic aromatic substitution) ortho and para carbon atoms of phenol can be defined as [$(c1c([OH])cccc1),$(c1ccc([OH])cc1)].
The definitions of hydrogen bond donors and acceptors used to apply Lipinski's Rule of Five[6] are easily coded in SMARTS.
The REOS (rapid elimination of swill) [8] procedure uses SMARTS to filter out reactive, toxic and otherwise undesirable moieties from databases of chemical structures.
RECAP is a molecule editor which generates fragments of structures by breaking bonds of defined types and the original link points in these are specified using isotopic labels.
Searching databases of biologically active compounds for occurrences of fragments allows privileged structural motifs to be identified.
The Molecular Slicer [10] is similar to RECAP and has been used to identify fragments that are commonly found in marketed oral drugs.
Leatherface can be used to standardise tautomeric and ionization states and to set and enumerate these in preparation of databases[12] for virtual screening.
A key problem in pharmacophore matching is that functional groups that are likely to be ionised at physiological pH are typically registered in their neutral forms in structural databases.