What is SMILES?

Learning objectives

After reading this article you will be able to:

  • Read and write simple SMILES strings
  • Explain canonical and isomeric SMILES
  • Know when SMILES is the wrong format

SMILES (Simplified Molecular Input Line Entry System), introduced by David Weininger in 1988, describes a molecule’s structure as a single line of text. It is compact, human-readable once you know the rules, and supported by almost every chemistry tool.

The basic rules

RuleExampleMolecule
Atoms are element symbols; hydrogens are impliedCCOEthanol
= double bond, # triple bondC=O, C#NFormaldehyde, hydrogen cyanide
Parentheses mark branchesCC(C)OIsopropanol
Matching digits close ringsC1CCCCC1Cyclohexane
Lower-case letters are aromatic atomsc1ccccc1Benzene
Square brackets for charges, isotopes and unusual atoms[NH4+]Ammonium

Putting these together, aspirin is CC(=O)Oc1ccccc1C(=O)O.

Canonical SMILES

The same molecule can be written many ways — ethanol is CCO or OCC. A canonical SMILES algorithm always produces one standard string for a given structure, which allows exact matching and duplicate removal in databases. Canonical forms differ between toolkits, so compare strings generated by the same software (for example RDKit).

Stereochemistry: isomeric SMILES

Isomeric SMILES adds 3D configuration: @ and @@ mark tetrahedral stereocentres, and / and mark double-bond geometry. Stereoisomers can have very different biological activity, so exact-match searches should compare isomeric forms.

Limits of SMILES

  • It carries no 3D coordinates; docking and modelling need a 3D conformer generated from it, or formats such as SDF/MOL.
  • Tautomers and charge states can be written in several valid ways, so standardise molecules before comparing them.
  • Very large biomolecules are better described with sequence or structure formats; see PDB and mmCIF.

Last updated October 31, 2026

Keep learning

What is a molecular fingerprint? A molecular fingerprint encodes a molecule's structural features as a fixed-length bit or count vector so that millions of molecules can be compared quickly. What is Tanimoto similarity? Tanimoto similarity compares two molecular fingerprints as shared features divided by total features, giving a score from 0 (nothing in common) to 1 (identical fingerprints). What is substructure search? Substructure search finds every molecule in a library that contains a given fragment or pattern, such as a ring system or functional group.

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