Cyclic amide regognized as amines

Computer-Aided Drug Design at the Durrant Lab Forums Dimorphite-DL Cyclic amide regognized as amines

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    • #15905 Reply
      Andrey Frolov
      Guest

      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

    • #63437 Reply
      Zhenting Gao
      Guest

      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

    • #134823 Reply
      Phillip Gingrich
      Guest

      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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