chembl-gen-check 0.1.4

Simple package that performs basic molecular structural sanity checks

chembl_gen_check

chembl_gen_check is a Python library for rapidly assessing how reasonable a (generated) molecule is. It ships with precomputed databases for both ChEMBL (medicinal chemistry from the scientific literature) and SureChEMBL (chemical structures extracted from patent literature), so no downloads or preprocessing are required: just pick one when loading your checker.

Using lightweight MolBloom filters, it verifies whether a compound's scaffolds, generic scaffolds or ring systems already exist in the selected database. It can also flag uncommon bonds via the LACAN algorithm and report structural alerts. Taken together, these checks give a fast read on the plausibility of a molecule's ring systems and scaffolds, and ensure that its atom and bond environments have precedent.

Installation

pip install chembl-gen-check

Usage example

from chembl_gen_check import Checker

checker = Checker("chembl")
#checker = Checker("surechembl")

smiles = "CCN(CC)C(=O)C[C@H]1C[C@@H]1c1ccccc1"
checker.load_smiles(smiles)

# Murcko scaffold found in the loaded database (True/False)
checker.check_scaffold()

# Generic Murcko scaffold found in loaded database (True/False)
checker.check_skeleton()

# All molecule ring systems found in loaded database (True/False)
checker.check_ring_systems()

# Number of structural alerts using the ChEMBL set in RDKit(integer)
checker.check_structural_alerts()

# LACAN hard pass/fail filter (default mode="threshold"): reject if any bond's
# PMI is below the threshold t (default 0.05). Returns 1.0 (pass) or 0.0 (fail).
checker.check_lacan()

How LACAN Works

Reference: Dehaen, W. LACAN. ChemRxiv preprint.

LACAN scores a molecule one bond at a time. Each bond is split into its two atom environments, and a PMI ratio (pointwise mutual information) is computed from the reference database:

PMI = P(env_a, env_b) / (P(env_a) * P(env_b))

that is, how often the two halves are actually bonded together versus how often they would be by pure chance. PMI > 1 means the bond is more common than chance, PMI ≈ 1 is as expected, and PMI ≈ 0 flags a junction that is essentially never seen in the database (a likely artifact).

A molecule is summarized by its weakest bond, min_PMI:

• mode="threshold"(default): a single bond is enough to fail the whole molecule — if any bond has PMI < t (default 0.05) it returns 0.0 (fail), otherwise 1.0 (pass).
• mode="score" : returns min_PMI / (1 + min_PMI), a value in [0, 1). Higher is more reasonable; 0.5 corresponds to min_PMI = 1.

Code to extract ring systems adapted from: W Patrick Walters. useful_rdkit_utils

Code to calculate LACAN scores adapted from: Dehaen, W. LACAN. https://github.com/dehaenw/lacan/