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Interfacing RDKit and AutoDock
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TypeError: unsupported operand type(s) for *: 'object' and 'Forward' #101

Closed HaoLan-compchem closed 3 days ago

HaoLan-compchem commented 5 months ago

Dear Meeko developer,

I tried to generate pdbqt file for a covalent ligand following the tutorial. The example was from https://autodock.scripps.edu/resources/covalent-docking/ (those are based on old python2 scripts... so I am seeking help from Meeko)

My command is:

mk_prepare_ligand.py \ -i ligand.sdf \ --receptor 3upo_protein.pdb \ --rec_residue "B:SER:222" \ --tether_smarts "C(=O)-O-C" \ --tether_smarts_indices 4 3 \ -o prepared.pdbqt

However I got such error:

CovalentBuilder> searching for residue: chid B and resname SER and resnum 222 and (name CA or name CB) Traceback (most recent call last): File "/home/haolan/miniconda3/bin/mk_prepare_ligand.py", line 312, in covalent_builder = CovalentBuilder(rec_prody_mol, args.rec_residue) File "/home/haolan/miniconda3/lib/python3.10/site-packages/meeko/covalentbuilder.py", line 63, in init out = self._generate_prody_selection(selection_tuple) File "/home/haolan/miniconda3/lib/python3.10/site-packages/meeko/covalentbuilder.py", line 80, in _generate_prody_selection found = self.rec.select( sel_string ) File "/home/haolan/miniconda3/lib/python3.10/site-packages/prody/atomic/atomic.py", line 232, in select return SELECT.select(self, selstr, kwargs) File "/home/haolan/miniconda3/lib/python3.10/site-packages/prody/atomic/select.py", line 895, in select indices = self.getIndices(atoms, selstr, kwargs) File "/home/haolan/miniconda3/lib/python3.10/site-packages/prody/atomic/select.py", line 953, in getIndices torf = self.getBoolArray(atoms, selstr, *kwargs) File "/home/haolan/miniconda3/lib/python3.10/site-packages/prody/atomic/select.py", line 1004, in getBoolArray parser = self._getParser(selstr) File "/home/haolan/miniconda3/lib/python3.10/site-packages/prody/atomic/select.py", line 1103, in _getParser parser.enablePackrat() File "/home/haolan/miniconda3/lib/python3.10/site-packages/pyparsing/util.py", line 265, in _inner return fn(args, *kwargs) File "/home/haolan/miniconda3/lib/python3.10/site-packages/pyparsing/core.py", line 1132, in enable_packrat ParserElement.packrat_cache = _FifoCache(cache_size_limit) # type: ignore[assignment] File "/home/haolan/miniconda3/lib/python3.10/site-packages/pyparsing/util.py", line 105, in init keyring = [object()] size TypeError: can't multiply sequence by non-int of type 'Forward'

I also tried the example from Meeko (bash script as provided), the exact same error was given...

Any solutions for this? Thank you very much

rwxayheee commented 5 months ago

Hi @HaoLan-compchem According to the README. For --tether_smarts_indices, the first index defines the C-alpha, and the second index defines the C-beta.

Is your ligand connected to the serine residue through an acyl group? Try this: 

--tether_smarts "C(=O)OCC" \
--tether_smarts_indices 5 4 \

And make sure your ligand contains this substructure. In this substructure, the 5th atom corresponds to C-alpha and the 4th atom corresponds to C-beta

HaoLan-compchem commented 5 months ago

Hi @HaoLan-compchem According to the README. For --tether_smarts_indices, the first index defines the C-alpha, and the second index defines the C-beta.

Is your ligand connected to the serine residue through an acyl group? Try this:

--tether_smarts "C(=O)OCC" \
--tether_smarts_indices 5 4 \

And make sure your ligand contains this substructure. In this substructure, the 5th atom corresponds to C-alpha and the 4th atom corresponds to C-beta

Not working, same error...

Here is my ligand sdf file containing Ca and Cb:

Penicillin PyMOL2.5 3D 0

50 51 0 0 0 0 0 0 0 0999 V2000 5.3493 2.9414 -2.0384 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9239 4.3300 -1.0838 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7379 2.7539 -0.9413 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7779 3.2498 -1.0848 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1379 -2.7870 0.2309 N 0 3 0 0 0 0 0 0 0 0 0 0 2.8211 -1.2229 1.0721 N 0 0 0 0 0 0 0 0 0 0 0 0 5.8407 -3.2810 1.4152 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8231 2.8589 0.0585 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1151 0.8346 1.1599 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1608 -0.6775 1.2522 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1976 -1.3147 0.2726 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2100 -2.5510 1.4556 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2617 -3.1880 0.5245 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7493 -2.4908 2.8948 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9244 -4.7949 1.4451 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0787 -1.0716 -0.0606 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6891 -1.6658 -0.1020 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0478 -1.4272 -1.3975 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4334 -1.9719 -2.6005 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2624 -1.7614 -3.7953 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4398 -1.0080 -3.7976 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9247 -0.4644 -2.6052 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2343 -0.6733 -1.4080 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8533 1.4904 0.2249 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3922 1.4582 1.9255 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4244 -5.3622 2.4028 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5193 -0.4503 -1.0172 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4335 -5.5269 0.4252 O 0 5 0 0 0 0 0 0 0 0 0 0 6.8837 -0.8575 0.8372 S 0 0 0 0 0 0 0 0 0 0 0 0 4.4789 -0.9224 2.2883 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0201 -0.9443 -0.7612 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1528 3.3672 0.9898 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7958 3.1892 -0.2072 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9135 -3.2171 -0.5279 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5019 -4.2235 0.8459 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2038 -2.5992 0.5552 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0153 -1.9917 3.5639 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6954 -1.9103 2.9309 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9509 -3.5077 3.2905 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4095 -1.7434 1.8615 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1197 -1.2233 0.7440 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7562 -2.7614 0.0699 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3422 -2.5612 -2.6083 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1099 -2.1843 -4.7193 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9776 -0.8469 -4.7227 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8372 0.1176 -2.6076 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6234 -0.2484 -0.4909 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2390 -2.9858 2.3027 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1558 -3.1425 0.1782 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6397 -3.1109 -0.6295 H 0 0 0 0 0 0 0 0 0 0 0 0 1 4 1 0 0 0 0 2 4 1 0 0 0 0 3 4 1 0 0 0 0 5 7 1 0 0 0 0 5 11 1 0 0 0 0 5 49 1 0 0 0 0 5 50 1 0 0 0 0 6 10 1 0 0 0 0 6 16 1 0 0 0 0 6 40 1 0 0 0 0 7 12 1 0 0 0 0 7 15 1 0 0 0 0 7 48 1 0 0 0 0 4 8 1 0 0 0 0 8 24 1 0 0 0 0 8 32 1 0 0 0 0 8 33 1 0 0 0 0 9 10 1 0 0 0 0 9 24 1 0 0 0 0 9 25 2 0 0 0 0 10 11 1 0 0 0 0 10 30 1 0 0 0 0 11 29 1 0 0 0 0 11 31 1 0 0 0 0 12 13 1 0 0 0 0 12 14 1 0 0 0 0 12 29 1 0 0 0 0 13 34 1 0 0 0 0 13 35 1 0 0 0 0 13 36 1 0 0 0 0 14 37 1 0 0 0 0 14 38 1 0 0 0 0 14 39 1 0 0 0 0 15 26 4 0 0 0 0 15 28 4 0 0 0 0 16 17 1 0 0 0 0 16 27 2 0 0 0 0 17 18 1 0 0 0 0 17 41 1 0 0 0 0 17 42 1 0 0 0 0 18 19 4 0 0 0 0 18 23 4 0 0 0 0 19 20 4 0 0 0 0 19 43 1 0 0 0 0 20 21 4 0 0 0 0 20 44 1 0 0 0 0 21 22 4 0 0 0 0 21 45 1 0 0 0 0 22 23 4 0 0 0 0 22 46 1 0 0 0 0 23 47 1 0 0 0 0 M END $$$$

And the command:

mk_prepare_ligand.py -i ligand_1.sdf --receptor 3upo_protein.pdb --rec_residue "B:SER:222" --tether_smarts "C(=O)OCC" --tether_smarts_indices 5 4 -o prepared.pdbqt

rwxayheee commented 5 months ago

Hi @HaoLan-compchem

Not sure if this is what you need but I was able to generate a prepared.pdbqt: 

BEGIN_RES B SER 222
REMARK SMILES CCOC(=O)[C@@H](NC(=O)Cc1ccccc1)[C@@H]1[NH2+][C@@H](C(:O):[O-])C(C)(C)S1
REMARK SMILES IDX 1 1 2 2 3 3 4 4 5 5 6 6 7 7 8 8 9 10 10 11 11 12 12 13 16 14
REMARK SMILES IDX 13 15 15 16 14 17 17 18 18 19 26 20 19 21 23 24 24 25 25 26
REMARK SMILES IDX 20 27 21 28 22 29
REMARK H PARENT 7 9 18 22 18 23
REMARK Flexibility Score: inf
ROOT
ATOM      1  CA  UNL     1      17.947 -69.887   9.246  1.00  0.00     0.049 C 
ENDROOT
BRANCH   1   2
ATOM      2  CB  UNL     1      17.494 -68.558   8.615  1.00  0.00     0.229 C 
BRANCH   2   3
ATOM      3  O   UNL     1      18.553 -67.996   7.933  1.00  0.00    -0.464 OA
BRANCH   3   4
ATOM      4  C   UNL     1      18.470 -66.815   7.266  1.00  0.00     0.335 C 
ATOM      5  O   UNL     1      17.412 -66.200   7.227  1.00  0.00    -0.249 OA
BRANCH   4   6
ATOM      6  C   UNL     1      19.690 -66.233   6.580  1.00  0.00     0.262 C 
BRANCH   6   7
ATOM      7  N   UNL     1      19.975 -64.910   7.121  1.00  0.00    -0.337 N 
ATOM      8  C   UNL     1      20.291 -64.668   8.425  1.00  0.00     0.225 C 
ATOM      9  H   UNL     1      19.919 -64.109   6.474  1.00  0.00     0.164 HD
ATOM     10  O   UNL     1      20.356 -65.584   9.232  1.00  0.00    -0.275 OA
BRANCH   8  11
ATOM     11  C   UNL     1      20.536 -63.241   8.859  1.00  0.00     0.135 C 
BRANCH  11  12
ATOM     12  C   UNL     1      20.865 -63.087  10.324  1.00  0.00    -0.039 A 
ATOM     13  C   UNL     1      22.036 -63.656  10.854  1.00  0.00     0.004 A 
ATOM     14  C   UNL     1      20.010 -62.356  11.168  1.00  0.00     0.004 A 
ATOM     15  C   UNL     1      22.344 -63.496  12.209  1.00  0.00     0.000 A 
ATOM     16  C   UNL     1      20.322 -62.202  12.522  1.00  0.00     0.000 A 
ATOM     17  C   UNL     1      21.488 -62.771  13.042  1.00  0.00     0.000 A 
ENDBRANCH  11  12
ENDBRANCH   8  11
ENDBRANCH   6   7
BRANCH   6  18
ATOM     18  C   UNL     1      20.930 -67.180   6.641  1.00  0.00     0.277 C 
ATOM     19  N   UNL     1      22.166 -66.562   6.127  1.00  0.00    -0.325 N 
ATOM     20  S   UNL     1      20.587 -68.652   5.600  1.00  0.00    -0.084 SA
ATOM     21  C   UNL     1      22.101 -66.620   4.666  1.00  0.00     0.246 C 
ATOM     22  H   UNL     1      22.297 -65.586   6.478  1.00  0.00     0.347 HD
ATOM     23  H   UNL     1      22.980 -67.132   6.459  1.00  0.00     0.347 HD
ATOM     24  C   UNL     1      21.740 -68.083   4.295  1.00  0.00     0.073 C 
ATOM     25  C   UNL     1      22.958 -69.028   4.311  1.00  0.00     0.030 C 
ATOM     26  C   UNL     1      21.049 -68.139   2.922  1.00  0.00     0.030 C 
BRANCH  21  27
ATOM     27  C   UNL     1      23.362 -66.089   4.012  1.00  0.00     0.101 C 
ATOM     28  O   UNL     1      23.436 -66.010   2.797  1.00  0.00    -0.544 OA
ATOM     29  O   UNL     1      24.404 -65.684   4.766  1.00  0.00    -0.544 OA
ENDBRANCH  21  27
ENDBRANCH   6  18
ENDBRANCH   4   6
ENDBRANCH   3   4
ENDBRANCH   2   3
ENDBRANCH   1   2
END_RES B SER 222

Using your input (but I formatted it to be able to visualize it): 

Penicillin
  PyMOL2.5 3D 0

 50 51  0  0  0  0  0  0  0  0999 V2000
    5.3493    2.9414   -2.0384 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.9239    4.3300   -1.0838 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.7379    2.7539   -0.9413 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.7779    3.2498   -1.0848 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1379   -2.7870    0.2309 N   0  3  0  0  0  0  0  0  0  0  0  0
    2.8211   -1.2229    1.0721 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.8407   -3.2810    1.4152 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8231    2.8589    0.0585 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1151    0.8346    1.1599 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1608   -0.6775    1.2522 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1976   -1.3147    0.2726 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2100   -2.5510    1.4556 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2617   -3.1880    0.5245 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7493   -2.4908    2.8948 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9244   -4.7949    1.4451 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0787   -1.0716   -0.0606 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6891   -1.6658   -0.1020 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0478   -1.4272   -1.3975 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4334   -1.9719   -2.6005 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2624   -1.7614   -3.7953 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4398   -1.0080   -3.7976 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9247   -0.4644   -2.6052 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2343   -0.6733   -1.4080 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8533    1.4904    0.2249 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.3922    1.4582    1.9255 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.4244   -5.3622    2.4028 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.5193   -0.4503   -1.0172 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.4335   -5.5269    0.4252 O   0  5  0  0  0  0  0  0  0  0  0  0
    6.8837   -0.8575    0.8372 S   0  0  0  0  0  0  0  0  0  0  0  0
    4.4789   -0.9224    2.2883 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.0201   -0.9443   -0.7612 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.1528    3.3672    0.9898 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.7958    3.1892   -0.2072 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.9135   -3.2171   -0.5279 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.5019   -4.2235    0.8459 H   0  0  0  0  0  0  0  0  0  0  0  0
    9.2038   -2.5992    0.5552 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.0153   -1.9917    3.5639 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.6954   -1.9103    2.9309 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.9509   -3.5077    3.2905 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.4095   -1.7434    1.8615 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.1197   -1.2233    0.7440 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.7562   -2.7614    0.0699 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.3422   -2.5612   -2.6083 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.1099   -2.1843   -4.7193 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9776   -0.8469   -4.7227 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8372    0.1176   -2.6076 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6234   -0.2484   -0.4909 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.2390   -2.9858    2.3027 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.1558   -3.1425    0.1782 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.6397   -3.1109   -0.6295 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  4  1  0  0  0  0
  2  4  1  0  0  0  0
  3  4  1  0  0  0  0
  5  7  1  0  0  0  0
  5 11  1  0  0  0  0
  5 49  1  0  0  0  0
  5 50  1  0  0  0  0
  6 10  1  0  0  0  0
  6 16  1  0  0  0  0
  6 40  1  0  0  0  0
  7 12  1  0  0  0  0
  7 15  1  0  0  0  0
  7 48  1  0  0  0  0
  4  8  1  0  0  0  0
  8 24  1  0  0  0  0
  8 32  1  0  0  0  0
  8 33  1  0  0  0  0
  9 10  1  0  0  0  0
  9 24  1  0  0  0  0
  9 25  2  0  0  0  0
 10 11  1  0  0  0  0
 10 30  1  0  0  0  0
 11 29  1  0  0  0  0
 11 31  1  0  0  0  0
 12 13  1  0  0  0  0
 12 14  1  0  0  0  0
 12 29  1  0  0  0  0
 13 34  1  0  0  0  0
 13 35  1  0  0  0  0
 13 36  1  0  0  0  0
 14 37  1  0  0  0  0
 14 38  1  0  0  0  0
 14 39  1  0  0  0  0
 15 26  4  0  0  0  0
 15 28  4  0  0  0  0
 16 17  1  0  0  0  0
 16 27  2  0  0  0  0
 17 18  1  0  0  0  0
 17 41  1  0  0  0  0
 17 42  1  0  0  0  0
 18 19  4  0  0  0  0
 18 23  4  0  0  0  0
 19 20  4  0  0  0  0
 19 43  1  0  0  0  0
 20 21  4  0  0  0  0
 20 44  1  0  0  0  0
 21 22  4  0  0  0  0
 21 45  1  0  0  0  0
 22 23  4  0  0  0  0
 22 46  1  0  0  0  0
 23 47  1  0  0  0  0
M  END
$$$$

My command is the same. The version of Meeko I used was:

0.5.0

Input and output in command prompt: 

(my-rdkit-env) amyhe@Amys-MBP Downloads % mk_prepare_ligand.py -i Penicillin.sdf --receptor 3upo_protein.pdb --rec_residue "B:SER:222" --tether_smarts "C(=O)OCC" --tether_smarts_indices 5 4 -o prepared.pdbqt
/opt/homebrew/anaconda3/envs/my-rdkit-env/lib/python3.12/site-packages/dateutil/tz/tz.py:37: DeprecationWarning: datetime.datetime.utcfromtimestamp() is deprecated and scheduled for removal in a future version. Use timezone-aware objects to represent datetimes in UTC: datetime.datetime.fromtimestamp(timestamp, datetime.UTC).
  EPOCH = datetime.datetime.utcfromtimestamp(0)
@> 6464 atoms and 1 coordinate set(s) were parsed in 0.03s.
CovalentBuilder> searching for residue: chid B and resname SER and resnum 222 and (name CA or name CB)
[10:51:25] Warning: molecule is tagged as 2D, but at least one Z coordinate is not zero. Marking the mol as 3D.
yipy0005 commented 5 months ago

I'm having the same problem as well. I'm using meeko 0.5.0 and prody 2.4.1. I have tried the same thing on a Linux machine, it's the same error too.

diogomart commented 3 days ago

It is caused by some incompatibility between prody and pyparsing, downgrading pyparsing to <3.1 fixes the issue.