AURORA Tutorial
Auditable Unified Retrieval and Optimization of Rational Analogs
Before proceeding with the molecule generation and searching, you need to Sign In and obtain your API key.
1. Molecule Generation
Overview:
This tool transforms one molecule (source) into another (target) by generating chemically valid intermediate structures. It identifies a common core between the two molecules and progressively modifies the structure while logging all intermediates.
Requirements:
- (i)Source SMILES: Your starting molecule
- (ii)Target SMILES: Your desired end molecule
*Preferably, the molecules with the known and desired activity
Outcome:
A CSV file containing following columns:
- (i)smiles: SMILES string of the generated molecule
- (ii)sa_score: Synthetic Accessibility score of the generated molecule
- (iii)sim_source: Similarity of the generated molecule to the Source
- (iv)sim_target: Similarity of generated molecule to Target
- (v)composite_score: Quality score assigned to the particular molecule.
Important Parameters:
(i) Search Parameters
| Parameter | Description | Default Value | Typical Range |
|---|---|---|---|
| BEAM_SIZE | Controls search breadth (higher = more exploration but slower) | 200 | 200 – 5000 |
| EPSILON | Exploration rate for diversity (higher = more random sampling) | 0.15 | 0.05 – 0.25 |
| SIM_THRESHOLD | Similarity threshold for early stopping (%) i.e similarity of generated molecule to Target | 95 | 90 – 99 |
| MAX_STEPS | Maximum number of search steps | 10000 | - |
(ii) Scoring Weights (Composite Score = α · Sim_target - β · SA + γ · Sim_source):
| Symbol | Parameter | Meaning | Default |
|---|---|---|---|
| α | ALPHA | Importance of reaching target | 1.0 |
| β | BETA | Penalty for poor synthetic accessibility | 0.1 |
| γ | GAMMA | Encouragement to stay near source | 0.5 |
Important Considerations:
- •Valid SMILES: Ensure both input SMILES are chemically valid
- •Shared Structure: Works best when molecules share a common core
- •Adjust Weights: Customize α, β, γ based on whether you prioritize reaching target, synthetic feasibility, or staying close to source
2. Database Search
This module automatically searches the generated molecules in the desired databases. We provide you with two choices of the database:
- (i)ZINC
- (ii)ChemBL
Input:
The csv file generated via molecule generation pipeline.
Output:
The csv file with few additional columns such as:
- (i)Hit1(smiles, ZINCID, MW, Tanimoto), Hit2(smiles, ZINCID, MW, Tanimoto) and so on.
Where,
- •smiles - SMILES of the found hit molecule
- •ZINCID - ID associated with the found molecule
- •MW - Molecular weight of the found molecule
- •Tanimoto - Tanimoto similarity between the found Hit and the query molecule.
User-defined Tanimoto score:
Set this according to your requirements. 1.0 means searching for molecules that are exactly similar.