Hi all,

I have looked at many papers and datasets, and realized that the definition and/or labelling of sites of metabolism is often used differently. Molecules with a tertiary aliphatic amine, such as amitriptyline, illustrate this. While Zaretzki dataset (doi: 10.1093/bioinformatics/bts705) identify the carbons atom C20 and C21 (adjacent to the N19 atom of the Nitrogen group), Rudik et al. (doi:  10.1186/s13321-016-0183-x) identify the Nitrogen atom (N19) as the site of metabolism. This is one of the possible scenarios where the definition/labelling of sites of metabolism becomes ambiguous. That being said, upon dealkylation, the C20, and C21 are all oxidized.

1) Is N19 the only SoM for the N-dealkylation? Are C20 and C21 SoMs for the N-dealkylation? Are all of them SoMs? If we take into account the fact that there are also often discrepancies in the annotation of the same set, it makes things even more complex.

2) If we rather look at bonds (e.g. N19-C20, and N19-C21) as sites of metabolism, it might become a bit less confusing.

Attached are the two annotations for the molecule amitriptyline.

What do you think?

Finding a consensus definition, and labelling sets in the same way would make it easier to generate more accurate predictive models, and to compare them with each other.

Thank you for your consideration.

Best,

Yannick

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