The script finds CHEMBL939 in the TSV file and uses its canonical_smiles as the reference. It then makes a second streaming pass through the file, generates Morgan fingerprints (radius=2, fpSize=2048), and ranks the remaining valid SMILES by Tanimoto similarity. Invalid SMILES and CHEMBL939 itself are skipped. Only the best 20 results (or the value passed to --top) are kept in memory.

Installation

python -m venv .venv
source .venv/bin/activate
pip install -r requirements.txt

RDKit can also be installed through conda-forge:

conda install -c conda-forge rdkit

Usage

python scimesh.py chembl_37_chemreps.txt -o gefitinib_similarities.csv

By default, the script writes a CSV with rank,chembl_id,canonical_smiles,similarity columns and prints the same top 20 results to the terminal. To choose a different number of results:

python scimesh.py chembl_37_chemreps.txt --top 50 -o top_50.csv

During the search, status is written to stderr every 100,000 rows: number of processed rows, current and average rates, elapsed time, and the number of invalid SMILES skipped. The interval can be changed or disabled:

python scimesh.py chembl_37_chemreps.txt --progress-every 500000
python scimesh.py chembl_37_chemreps.txt --progress-every 0

Quick test on part of the database

The --max-rows option limits the second pass to the first N TSV rows. CHEMBL939 is still found in its own streaming pass first, so the reference stays the same. The resulting CSV is the top 20 only within the processed subset, not the full database.

python scimesh.py chembl_37_chemreps.txt --max-rows 10000 -o test_results.csv

Structure images

Pass a directory to --images-dir to create CHEMBL939_gefitinib.png for gefitinib and top_candidates.png with a grid of top candidates. Candidate images show rank, ChEMBL ID, and Tanimoto similarity.

python scimesh.py chembl_37_chemreps.txt --images-dir structures

The --image-columns option controls the number of structures per grid row (default: 4).