Tautomer Search

Tautomer search is a specialized task in computational chemistry that focuses on identifying the different tautomeric forms of a molecule. Tautomers are isomers that readily interconvert by the movement of a hydrogen atom and a double bond. This process is crucial in drug discovery and molecular modeling, as the tautomeric form of a molecule can significantly affect its biological activity, stability, and interaction with targets.

Our advanced tautomer search engine employs state-of-the-art algorithms to efficiently discover stable tautomers while ensuring comprehensive coverage of the tautomerism landscape.

Methodology

Tautomer generation happens after consecutive protonation and deprotonation site screening for a molecule. Centers for the protonation in the input molecular structure are determined and H⁺ ions are added to the π and lone pair centers. The geometries are then optimized with the molecular charge increased by one. From the initial geometries, protons are removed one-by-one and the resulting input geometries are optimized. Through the consecutive protonation and deprotonation steps, an ensemble of tautomers is formed.

Workflow Architecture

┌──────────────────────────────┐
│       **User Input**         │
├──────────────────────────────┤
│ Atomic coordinates           │
│ Charge and spin              │
│ Optional:*xtb* pre-optimized │
└────────────┬─────────────────┘
             │
             ▼
┌──────────────────────────────┐
│ **Workflow Initialization**  │
├──────────────────────────────┤
│ Identification and ranking   │
│ of protonation sites.        │
└────────────┬─────────────────┘
             │
             ▼
┌──────────────────────────────┐
│ **H⁺ Addition**              │
├──────────────────────────────┤
│ To the π and lone pair       │
│ centers                      │
└────────────┬─────────────────┘
             │
             ▼
┌──────────────────────────────┐
│ **Deprotonation**            │
├──────────────────────────────┤
│ Removal of protons from the  │
│ initial structure            │
└────────────┬─────────────────┘
             │
             ▼
┌──────────────────────────────┐
│ **Tautomer Ensemble Out**    │
├──────────────────────────────┤
│                              │
└──────────────────────────────┘

Input Configuration

The tautomer search requires minimal user input, emphasizing ease of use and automation:

Input Molecule

Upload your input molecule in a supported format (e.g., XYZ) or you can give a SMILES string. The system will automatically generate the initial conformer. Check the Input and Visualizer section for more details.

Model

Select the computational model for the conformer search. Options include:

GFN1
GFN2

Solvent

Choose the solvent model for the conformer search. Options include:

Gas phase (Keep it None)
Implicit solvent (e.g., water)