Cyclic amide regognized as amines

[Andrey Frolov]

Hi all,

Dimorphite-DL seems to confuse the cyclic amides with amines. E.g. see the test molecule below. These substructures used in cross-linking peptides known as TATA or TATB cores (https://pubs.acs.org/doi/10.1021/acs.accounts.7b00184), so they are not very exotic. Would be great if you could you propose a workaround. Thanks!

…/dimorphite_dl-1.2.4/dimorphite_dl.py –smiles ‘CC(=O)N1CN(CN(C1)C(C)=O)C(C)=O’

For help, use: python dimorphite_dl.py –help
t
If you use Dimorphite-DL in your research, please cite:
Ropp PJ, Kaminsky JC, Yablonski S, Durrant JD (2019) Dimorphite-DL: An
open-source program for enumerating the ionization states of drug-like small
molecules. J Cheminform 11:14. doi:10.1186/s13321-019-0336-9.

PARAMETERS:

label_states: False
max_ph: 8.4
max_variants: 128
min_ph: 6.4
output_file: None
pka_precision: 1.0
silent: False
smiles: CC(=O)N1CN(CN(C1)C(C)=O)C(C)=O
smiles_file: None
test: False

CC(=O)N1CN(C(C)=O)CN(C(C)=O)C1
CC(=O)N1CNH+CNH+C1
CC(=O)N1CN(C(C)=O)CNH+C1
CC(=O)[NH+]1CNH+CNH+C1

[Zhenting Gao]

I found similar bug as Andrey’s.

N in cyclic urea is protonated at pH=7.4.
Example molecule SMILES: CN1CCNC1=O

dimorphite_dl-1.2.4/dimorphite_dl.py –smiles CN1CCNC1=O –min_ph 7.4 –max_ph 7.4 –pka_precision 0.2

For help, use: python dimorphite_dl.py –help

If you use Dimorphite-DL in your research, please cite:
Ropp PJ, Kaminsky JC, Yablonski S, Durrant JD (2019) Dimorphite-DL: An
open-source program for enumerating the ionization states of drug-like small
molecules. J Cheminform 11:14. doi:10.1186/s13321-019-0336-9.

PARAMETERS:

label_states: False
max_ph: 7.4
max_variants: 128
min_ph: 7.4
output_file: None
pka_precision: 0.2
silent: False
smiles: CN1CCNC1=O
smiles_file: None
test: False

C[NH+]1CCNC1=O

[Phillip Gingrich]

Same, except it isn’t just cyclic amides. Dimethyl formamide and dimethyl acetamide are both protonated at a neutral pH.

If you remove one of the N-methyl groups, the amide is not protonated at neutral pH.

So at least from these limited tests, it seems to be related to if there are two alkyl substituents on the nitrogen.

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