In cheminformatics, effective representation of molecular structures is essential for data sharing, computational modeling, and database searching. SMILES (Simplified Molecular Input Line Entry System) and InChI (International Chemical Identifier) are two widely used notations, each with unique characteristics and applications. While SMILES is compact and intuitive, InChI is structured and algorithmically robust. This guide explores the relationship between these two formats, their strengths, and practical ways to interconvert them.


What Are SMILES and InChI?

  1. SMILES (Simplified Molecular Input Line Entry System)
    • Overview: A linear, human-readable string format for representing molecules.
    • Features:
      • Encodes atoms, bonds, and basic molecular connectivity.
      • Supports stereochemistry and isotopes.
    • Example: Benzene is represented as C1=CC=CC=C1.
  2. InChI (International Chemical Identifier)
    • Overview: A structured, non-proprietary text representation of chemical compounds.
    • Features:
      • Algorithmically generated from structural data.
      • Includes layers for connectivity, hydrogen atoms, stereochemistry, isotopes, and charge.
    • Example: Benzene is represented as InChI=1S/C6H6/c1-2-4-6-5-3-1/h1-6H.

Key Differences Between SMILES and InChI

AspectSMILESInChI
ReadabilityHuman-readable and intuitiveAlgorithmically generated
UniquenessNon-unique (depends on conventions)Unique (standardized)
AlgorithmDirectly written by users/toolsGenerated using a specific algorithm
ApplicationsIdeal for quick encoding and sharingSuitable for precise data storage and retrieval
File SizeCompact and conciseLonger due to detailed information

How Are SMILES and InChI Related?

SMILES and InChI both encode molecular structures, but their formats and purposes differ:

  • Structural Representation: Both capture molecular connectivity, but SMILES is flexible and user-oriented, while InChI is precise and standardized.
  • Interconversion: Tools like Open Babel and RDKit enable seamless conversion between SMILES and InChI, ensuring compatibility across applications.
  • Layered Data: InChI provides hierarchical information in layers, such as main structure, stereochemistry, and isotopes, which is implicit in SMILES.

Converting Between SMILES and InChI

  1. Using Open Babel Open Babel is an open-source cheminformatics toolkit that supports SMILES-InChI conversion.
    • SMILES to InChI:obabel -:"C1=CC=CC=C1" -oinchiOutput: InChI=1S/C6H6/c1-2-4-6-5-3-1/h1-6H
    • InChI to SMILES:obabel -iinchi "InChI=1S/C6H6/c1-2-4-6-5-3-1/h1-6H" -osmiOutput: c1ccccc1
  2. Using RDKit (Python Library)
    • SMILES to InChI:from rdkit import Chem smiles = "C1=CC=CC=C1" mol = Chem.MolFromSmiles(smiles) inchi = Chem.MolToInchi(mol) print(inchi)Output: InChI=1S/C6H6/c1-2-4-6-5-3-1/h1-6H
    • InChI to SMILES:inchi = "InChI=1S/C6H6/c1-2-4-6-5-3-1/h1-6H" mol = Chem.MolFromInchi(inchi) smiles = Chem.MolToSmiles(mol) print(smiles)Output: c1ccccc1

Practical Applications

  1. Database Integration
    • SMILES: Useful for input into software tools, molecule sketching, and cheminformatics pipelines.
    • InChI: Preferred for database indexing, searching, and retrieval due to its uniqueness and standardization.
  2. Chemical Informatics Workflows
    • Converting between formats ensures compatibility between tools like molecular modeling software and chemical databases.
  3. Drug Discovery
    • SMILES facilitates virtual screening and docking studies, while InChI aids in precise identification of compounds.

Best Practices

  1. Choose the Right Format: Use SMILES for quick, human-readable tasks and InChI for rigorous data storage and analysis.
  2. Validate Conversions: Always verify the correctness of interconverted strings using visualization tools.
  3. Leverage Tools: Utilize Open Babel, RDKit, and other software for efficient conversions.

Conclusion

Understanding the relationship between SMILES and InChI enables researchers to leverage their respective strengths in different contexts. Whether encoding simple molecules or managing complex databases, the ability to interconvert these formats ensures seamless data integration and enhances the efficiency of cheminformatics workflows. With tools like Open Babel and RDKit, mastering SMILES and InChI is both practical and indispensable for modern chemical research.


Further Resources