4 ms·
Exactly what I was thinking, especially for an entirely novel molecule. I wonder how novel the scaffold is. Whichever med chemist led this initiative is an arti
by whymauri 5y ago
Exactly what I was thinking, especially for an entirely novel molecule. I wonder how novel the scaffold is. Whichever med chemist led this initiative is an artist -- amazing job.
- dekhn 5y agoit's not hard to find other molecules with similar scaffolds. Simply train an unsupervised network (autoencoder) over SMILES strings taken from ZINC. Convert your molecule of interest to a vector using the encoder, then find N nearest neighbors and decode. Those molecules will likely have similar scaffolds. There are other methods, graph substructure similarity is common. More to your actual question, it was derived from a previous attempt (https://en.wikipedia.org/wiki/Lufotrelvir https://en.wikipedia.org/wiki/Lufotrelvir) which has a very similar structure, and I wasn't able to find prior information by doing a little literature searching to see if there are other similar compounds.
- whymauri 5y agoRight, it's not technically difficult to match a scaffold -- you can probably parallelize a big RDKit job, but it's nontrivial to scale to a gigascale set. And, like you mentioned, there's rule-based substructure matching (sometimes easier for those willing to venture a bit outside SMILES). Anyways, it was more a curiosity question -- thank you for the details on Lufotrelvir!
- dekhn 5y agoyou wouldn't run a big rdkit job, you'd just featurize all your molecules and then do vector comparisons. lots less CPU but a big risk of false negatives.
- whymauri 5y agowhat does 'featurize' mean here? do you mean fingerprint feature vectors? IIRC, the computation time to get a fingerprint vector vs. extracting a murcko scaffold are pretty similar, although it depends on the fingerprint.