ECFP invert

what's this

This is the algorithmic ECFP inversion approach developed in our lab (https://github.com/lich-uct). It is fully refactored from the previous version and has superior performance now. If you would like to use the old version anyway, you can find it here: https://github.com/dehaenw/ECFPinvert/tree/da6301b511d076b341da67d50bb9edd7691307dc

ECFP is a type of circular fingerprint used to encode the presence of substructures in molecules. In this prototype implementation we use RDKit's MorganFingerprint as our ECFP. By a fragment per fragment build up of the molecule and checking it at every step, a good degree of reconstruction is possible. An alternative NN based method for inversion was developed earlier and can be found here: https://github.com/bayer-science-for-a-better-life/neuraldecipher Their paper also contains some good background on why it is interesting to show some ECFP can be inverted.

installation

PIP environment setup

requires PIP within python 3.11 or lower. Then just:

conda create -n [environment_name] python=3.11  # or any other way to get python env 
git clone https://github.com/dehaenw/ECFPinvert
cd ECFPinvert
pip install .

manual environment setup

Alternatively, just make sure the conda env or venv has rdkit=2022.09 and numpy=1.23.4. Yes, it is important to have these exact versions (for now).

i want to try it

here is a minimally working code block to invert the ECFP4(2048) of strychnine, a rather complex molecule:

from rdkit import Chem
from search import ECFPInvert
import utils
utils.initialize_atomtypes("CHEMBL")
utils.set_fp_settings(2,2048)
strychnine = Chem.MolFromSmiles("C1CN2CC3=CCO[C@H]4CC(=O)N5[C@H]6[C@H]4[C@H]3C[C@H]2[C@@]61C7=CC=CC=C75")
strychnine_fp = utils.get_fp(strychnine)
inv = ECFPInvert()
s, info = inv.run_search(strychnine_fp)
if s:
    print(f'inverted strychnine in {info["time"]} seconds')
else:
    print("failure")

if that worked it should print something like inverted strychnine in 9.421 seconds

I will add example notebooks in a few days. Stay tuned!

what are the limitations and plans

Exact reconstruct only. Can't be used to reconstruct non existent fingerprints that do not correspond to a real structure. This version had ca 97% success inverting ChEMBL like ECFP6(4096).