Substructure search SMARTS

Key words Protein kinase, kinase-targeted library, library design, kinase chemical cores, substructure search, SMARTS Query, subsetting, binding mode annotation. 

Using simple rules, a structure is represented by a string of characters unique to that structure. It can also be used to specify stereochemistry at double bonds and chiral centres. SMARTS is a further extension that allows substructure searching. 

It is possible to specify the isotope of any atom in a SMILES string. This is generally not necessary because the most common isotope is simply assumed. But if, for example, a database contains information about 13C, this can be readily encoded into the SMILES using [13C] instead of simply C. The [13C] atom is considered different from the normal C atom in a SMILES. A direct lookup using canonical SMILES will not locate isotopes of the same structure. A substructure search using the matches function will locate isotopes. This is because the match function uses SMARTS to specify the desired substructure. 

As discussed above, hydrogen atoms are handled differently from other atoms in SMILES and SMARTS. When searching for structures matching CC all structures will be found that contain ethane as a substructure. Of course, this does not mean [CH3][CH3], but rather any two single-bonded carbon atoms with any number of H atoms attached. One could be more specific and search for, say, [CH][CH] to require exactly one H atom on each carbon. 

The align function can be expanded in many ways. For example, instead of simply finding the center of each molecule, a substructure could be used. This might be defined as a SMARTS match that is expected in each of the molecules to be aligned. This would be a natural outcome of a substructure search. In order to create an array of coordinates for a subset of a molecule, the following function could be used. 

Table A.4 shows commonly used fragment keys the MACCS publicl66-keys. This table is used with the publicl66keys function above to produce a bit string key for use in filtering before substructure searching and for similarity computations. The table consists of SMARTS patterns3 used to identify each of 166 substructures.

SMILES - simplified molecular line entry specification. A very terse linear notation which is much easier to create and to decode than the notorious WLN (Wiswesser line notation). Variations of SMILES include SSMILES, USMILES, SMARTS, SMIRKS, STRAPS, GHUGKLES, GHORTLES, and GHARTS which add features such as substructure search operators, reactions, combinatorial chemistry, and unique naming. ... 

The JME can also serve as a query input tool for structure databases by allowing creation of complex substructure queries (Figure 2-130), which are automatically translated into SMARTS [22]. With the help of simple HTML-format elements the creation of 3D structure queries is also possible, as were used in the 3D pharmacophore searches in the NCI database system [129]. Creation of reac-... 

With these sets of substructures and SMARTS queries, we searched our corporate compound collections and identified... 

SMARTS is a language that allows specifying substructures using rules that are straightforward extensions of the SMILES language. In addition, there are several other extensions of the algorithm, e.g., searching for sequences of amino acids, and for chemical reactions, both for reactants and educts. 

---