Simplified molecular input line entry specification



smiles
File extension:.smi
Type of format:chemical file format

The simplified molecular input line entry specification or SMILES is a specification for unambiguously describing the structure of molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules.

The original SMILES specification was developed by Arthur Weininger and David Weininger in the late 1980s. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems Inc. In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other 'linear' notations include the Wiswesser Line Notation (WLN), ROSDAL and SLN (Tripos Inc).

In August of 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI; it also has a wide base of software support with extensive theoretical (e.g., graph theory) backing.

Canonical SMILES and Isomeric SMILES

The terms Canonical and Isomeric can lead to some confusion when applied to SMILES. The terms describe different attributes of the SMILES and are not mutually exclusive.

Typically, a number of equally valid SMILES can be written for a molecule. For example, CCO, OCC and C(O)C all specify the structure of database.

SMILES notation allows the specification of configuration at tetrahedral centers, and double bond geometry. These are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed Isomeric SMILES. A notable feature of these rules is that they allow rigorous partial specification of chirality. SMILES in which isotopes are specified are also described as Isomeric SMILES.

Graph-based definition

In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph. The chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree.

Examples

Atoms

hydroxide anion is [OH-]. Brackets can be omitted for the "organic subset" of B, C, N, O, P, S, F, Cl, Br, and I. All other elements must be enclosed in brackets. If the brackets are omitted, the proper number of implicit hydrogen atoms is assumed; for instance the SMILES for water is simply O.

Bonds

Bonds between aliphatic atoms are assumed to be single unless specified otherwise and are implied by adjacency in the SMILES. For example the SMILES for hydrogen cyanide).

Branching

Branches are described with parentheses, as in CCC(=O)O for Dioxane can be written in SMILES notation as O(CCO1)CC1, O(C1)CCOC1, C(OCC1)CO1 or O1CCOCC1.

Aromaticity

imidazole is written in SMILES notation as n1c[nH]cc1.

The Daylight and OpenEye algorithms for generating canonical SMILES differ in their treatment of aromaticity.

Stereochemistry

Configuration around double bonds is specified using the characters "/" and "\". For example, F/C=C/F (see depiction)is one representation of trans-difluoroethene, in which the fluorine atoms are on opposite sides of the double bond, whereas F/C=C\F (see depiction) is one possible representation of cis-difluoroethene, in which the Fs are on the same side of the double bond, as shown in the figure.

Configuration at tetrahedral carbon is specified by @ or @@. L-Alanine, the more common alanine can be written as N[C@@H](C)C(=O)O (see depiction). The @@ specificer indicates that, when viewed from nitrogen along the bond to the chiral center, the substituents the sequence of substitients hydrogen (H), methyl (C) and carboxylate (C(=O)O)appear clockwise. D-Alanine can be written as N[C@H](C)C(=O)O (see depiction). The order of the substituents in the SMILES string is very important and D-alanine can also be encoded as N[C@@H](C(=O)O)C (see depiction).

Isotopes

benzene is [14c]1ccccc1 and deuterochloroform is [2H]C(Cl)(Cl)Cl.

Other Examples of SMILES

The SMILES notation is described extensively in the SMILES theory manual provided by Daylight Chemical Information Systems and a number of illustrative examples are presented. Daylight's depict utility provides users with the means to check their own examples of SMILES and is a valuable educational tool.

Extensions

chemical database search applications. This practice has led to a common misconception that chemical substructure search is achieved computationally by matching SMILES/SMARTS strings, when, in fact, it is achieved by the computationally more intensive search for subgraph isomorphism in the graphs reconstructed from the SMILES representations.

Conversion

SMILES can be converted back to 2-dimensional representations using Structure Diagram Generation algorithms (Helson, 1999). This conversion is not always unambiguous. Conversion to 3-dimensional representation is achieved by energy minimization approaches. There are many downloadable and web-based conversion utilities.

See also

References

  • Anderson, E.; Veith, G.D; Weininger, D. (1987) SMILES: A line notation and computerized interpreter for chemical structures. Report No. EPA/600/M-87/021. U.S. EPA, Environmental Research Laboratory-Duluth, Duluth, MN 55804
  • Weininger, D. (1988), SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules, J. Chem. Inf. Comput. Sci. 28, 31-36.
  • Weininger, D.; Weininger, A.; Weininger, J.L. (1989) SMILES. 2. Algorithm for generation of unique SMILES notation J. Chem. Inf. Comput. Sci. 29, 97-101.
  • Helson, H.E. (1999) Structure Diagram Generation In Rev. Comput. Chem. edited by Lipkowitz, K. B. and Boyd, D. B. Wiley-VCH, New York, pages 313-398.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Simplified_molecular_input_line_entry_specification". A list of authors is available in Wikipedia.