ionization states and tautomers of amide bonds

Computer-Aided Drug Design at the Durrant Lab Forums Gypsum-DL ionization states and tautomers of amide bonds

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      Loris Moretti
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      Hi,

      First of all, thanks for this software, I think a free tool that can be used by many and set a standard in the field is missing. I am evaluating it for implementation in my VS workflow and I have some issues with ionization states of groups. I have noticed wrongly assigned ionization to amides (protonated) and pyrazole like moieties (deprotonated). I have produced a test set, reported here:
      test set:
      ########################################
      O=C(c(cc1)c(F)c2c1[nH]nc2)N3CCCC3 test1
      NC(c(cc1)c(F)c2c1[nH]nc2)=O test2
      CNC(c1c(Cl)c(CNC(c2ccccc2)=O)ccc1)=O test3
      NC(c1c[nH]nc1)=O test4
      O=C(NC1CCCCC1)c2c[nH]nc2 test5
      O=C(NC1=CC=CC=C1)c2c[nH]nc2 test6
      Fc1ccc(C(N)=O)c2c1cn[nH]2 test7
      OC(CC(C1=CC=C(C=NN2)C2=C1)CC)=O test8
      CN1CCN(CC(N(C)C)=O)CC1 test9
      ########################################
      I have tested the default settings of Gypsum as well as various pH combination. Plus, following a question about ionization of phenol, tested these 2 conditions:
      –min_ph 7.0 –max_ph 7.0 –pka_precision 0.0
      –min_ph 7.4 –max_ph 7.4 –pka_precision 0.0
      I get very different results with the 2 command lines, even though the variation of the pH is small (0.4 unit).
      While if I use "–pka_precision 1" I have still the problem of deprotonation of the pyrazole like moieties and with the tautomers of the amides exchanging the H from the nitrogen to the oxygen, but also from the close carbon atom to the oxygen.

      Are you aware of these problems? Do you have any suggestions about flags in the command line to get more correct results?

      Best regards,
      Loris

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