Fuzzy Scaffolds¶

Fuzzy scaffolding is a concept useful for scaffold decoration and constrained scaffolding. If you want finer control over the generation of your scaffolds, you can use the fuzzy scaffold function to enforce specific groups that need to appear in the core as a sort of pharmacophore requirement.

Note: A pharmacophore is essentially “a part of a molecular structure that is responsible for a particular biological or pharmacological interaction that it undergoes”.

You can also force R groups to be included as well, allowing for flexibility to reconstruct specified positions (attachment points) in the scaffold. Overall, it allows you to build a highly specific molecular series to be used for MMPA.

Understanding Key Parameters¶

enforce_subs - this lets you specify what substructure(s) you want to enforce on the scaffold
n_atom_cuttoff - the minimum number of atoms a core should have. The smaller the number, the smaller the new scaffolds will be or the lesser number of new scaffolds will be generated, vice versa is true.
ignore_non_ring - Some scaffolds might be a simple aliphatic chain, in other words, a molecule that only contains straight/branched chains with no rings. Most of the time, you want to *ignore these scaffolds* as they typically don’t translate well in a drug-like context.
mcs_params - This is quite a niche parameter. If two molecules in your dataset have a different Murcko scaffold but the same Minimum Common scaffold, toggling this argument will categorize these molecules into the same bucket using a maximum common substructure algorithm.

Datamol Example¶

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import datamol as dm

# Get some mols
data = dm.data.cdk2()

data["mol"] = data["smiles"].apply(dm.to_mol)

dm.to_image(data["mol"].iloc[:12].tolist(), mol_size=(200, 150), use_svg=False)
import datamol as dm

# Get some mols
data = dm.data.cdk2()

data["mol"] = data["smiles"].apply(dm.to_mol)

dm.to_image(data["mol"].iloc[:12].tolist(), mol_size=(200, 150), use_svg=False)

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with dm.without_rdkit_log():
    scaffolds, scf2infos, scf2groups = dm.scaffold.fuzzy_scaffolding(data["mol"].tolist())

sfs = [dm.to_mol(s) for s in list(scaffolds)]
dm.to_image(sfs, mol_size=(200, 150), max_mols=12, use_svg=False)
with dm.without_rdkit_log():
    scaffolds, scf2infos, scf2groups = dm.scaffold.fuzzy_scaffolding(data["mol"].tolist())

sfs = [dm.to_mol(s) for s in list(scaffolds)]
dm.to_image(sfs, mol_size=(200, 150), max_mols=12, use_svg=False)

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