Hi Rafael,
thanks for the tip. For some cases filtering out the small fragments would
work. The problem is that sometimes the small fragment is making
interactions with the binding pocket that I want to keep. Like in the
example below, Chem.FragmentOnBRICSBonds will generate nine fragments.
Among these are the tetrazole and chlorophenyl groups.
mol="""1sl3
3D
Schrodinger Suite 2020-3.
37 40 0 0 1 0 999 V2000
19.8850 -14.4930 26.0920 C 0 0 0 0 0 0
19.8090 -15.8920 25.7160 C 0 0 0 0 0 0
20.8840 -16.4990 25.0550 N 0 3 0 0 0 0
22.0630 -15.8640 24.6980 C 0 0 0 0 0 0
22.1840 -14.4770 25.0450 C 0 0 0 0 0 0
21.0990 -13.8170 25.7440 C 0 0 0 0 0 0
18.5420 -16.7220 25.9220 C 0 0 0 0 0 0
17.9270 -17.1560 24.6050 C 0 0 0 0 0 0
17.2390 -16.0490 23.9180 N 0 0 0 0 0 0
17.9430 -15.3750 22.8840 C 0 0 0 0 0 0
17.4220 -14.1380 22.2760 C 0 0 0 0 0 0
18.1450 -13.5090 21.2900 N 0 0 0 0 0 0
19.4450 -13.9240 20.8140 C 0 0 0 0 0 0
19.9520 -15.0780 21.4460 C 0 0 0 0 0 0
19.2190 -15.7850 22.3930 N 0 0 0 0 0 0
16.3470 -13.6760 22.6470 O 0 0 0 0 0 0
20.2940 -13.0680 19.6270 Cl 0 0 0 0 0 0
17.6120 -12.2700 20.6890 C 0 0 0 0 0 0
16.1360 -12.4120 20.3520 C 0 0 0 0 0 0
15.3990 -11.3120 20.5550 N 0 0 0 0 0 0
15.6960 -13.4630 19.8970 O 0 0 0 0 0 0
13.9620 -11.3520 20.2480 C 0 0 0 0 0 0
13.1050 -11.3550 21.5070 C 0 0 0 0 0 0
13.0960 -10.1610 22.3090 C 0 0 0 0 0 0
12.2840 -10.1950 23.4950 C 0 0 0 0 0 0
11.5040 -11.3370 23.8990 C 0 0 0 0 0 0
12.3340 -12.4970 21.9000 C 0 0 0 0 0 0
11.5100 -12.5220 23.0980 C 0 0 0 0 0 0
18.8320 -17.8780 26.5420 F 0 0 0 0 0 0
17.6180 -16.0780 26.6550 F 0 0 0 0 0 0
12.2380 -8.7570 24.4850 Cl 0 0 0 0 0 0
20.7720 -17.8030 24.7230 O 0 5 0 0 0 0
13.2350 -15.7030 20.5450 N 0 0 0 0 0 0
12.3840 -15.2320 19.8030 N 0 0 0 0 0 0
11.9670 -14.1020 20.2010 N 0 0 0 0 0 0
12.4750 -13.6680 21.2150 N 0 0 0 0 0 0
13.3510 -14.7260 21.5840 C 0 0 0 0 0 0
1 2 1 0 0 0
1 6 2 0 0 0
2 3 2 0 0 0
2 7 1 0 0 0
3 4 1 0 0 0
3 32 1 0 0 0
4 5 2 0 0 0
5 6 1 0 0 0
7 8 1 0 0 0
7 29 1 0 0 0
7 30 1 0 0 0
8 9 1 0 0 0
9 10 1 0 0 0
10 11 1 0 0 0
10 15 2 0 0 0
11 12 1 0 0 0
11 16 2 0 0 0
12 13 1 0 0 0
12 18 1 0 0 0
13 14 2 0 0 0
13 17 1 0 0 0
14 15 1 0 0 0
18 19 1 0 0 0
19 20 1 0 0 0
19 21 2 0 0 0
20 22 1 0 0 0
22 23 1 0 0 0
23 24 2 0 0 0
23 27 1 0 0 0
24 25 1 0 0 0
25 26 2 0 0 0
25 31 1 0 0 0
26 28 1 0 0 0
27 28 2 0 0 0
27 36 1 0 0 0
33 34 1 0 0 0
33 37 2 0 0 0
34 35 2 0 0 0
35 36 1 0 0 0
36 37 1 0 0 0
M CHG 2 3 1 32 -1
M END"""
m2 = Chem.MolFromMolBlock(mol)
newmol2=Chem.FragmentOnBRICSBonds(m2)
mfl=Chem.GetMolFrags(newmol2,asMols=True,sanitizeFrags=True)
Draw.MolsToGridImage(mfl,molsPerRow=4)
I would like to keep these two fragments connected, and I can do this with
the code below using BRICS.BRICSDecompose
frag = [Chem.MolFromSmiles(x) for x in sorted
(BRICS.BRICSDecompose(m3,minFragmentSize=6))]
Draw.MolsToGridImage(frag,molsPerRow=4)
What I didn't figure out yet is how to preserve the 3D coordinates when I
use BRICS.BRICSDecompose or how to make Chem.FragmentOnBRICSBonds generate
larger fragments
Best,
Renato
On Thu, Jul 14, 2022 at 9:39 AM Rafael L <[email protected]> wrote:
> Renato, it seems that FragmentOnBRICSBonds and BRICS.BRICSDecompose work
> differently. The first returns a mol object from which you can get the
> fragments using GetMolFrags (as you did), while the second returns a list
> of strings containing the fragments. I'm not sure if you can recover 3D
> info from these strings.
> If you want to get the fragments from BRICS.BRICSDecompose, use:
>
> l = BRICS.BRICSDecompose(m2,minFragmentSize=9)
> fr2 = [Chem.MolFromSmiles(x) for x in l]
> Draw.MolsToGridImage(fr2,molsPerRow=4)
>
>
> Alternatively, if you want to remove the small fragments obtained from
> FragmentOnBRICSBonds, you can filter by using the atom count:
>
> newmol2=Chem.FragmentOnBRICSBonds(m2)
> frags=Chem.GetMolFrags(newmol2,asMols=True,sanitizeFrags=True)
> frags = [x for x in frags if len(x.GetAtoms()) > 3]
> Draw.MolsToGridImage(frags,molsPerRow=4)
>
>
> On Wed, Jul 13, 2022 at 8:01 PM Renato Freitas <[email protected]>
> wrote:
>
>> Dear Rdkit team,
>>
>> I want to fragment a ligand from PDB and keep the 3D coordinates of the
>> resulting fragments. I was able to do that using the code below
>>
>> ###################
>> import rdkit
>> import py3Dmol
>> from rdkit import Chem
>> from rdkit.Chem import rdmolops
>> from rdkit import RDLogger
>> from rdkit.Chem import BRICS
>> from rdkit.Chem import Recap
>> from rdkit.Chem import Draw
>> from rdkit.Chem import AllChem
>> from rdkit.Chem.Draw import IPythonConsole
>> from rdkit import Chem, RDConfig
>> from rdkit.Chem import AllChem, rdMolAlign
>>
>> mol ="""rot-1A5H-A
>> RDKit 3D
>>
>> 28 30 0 0 1 0 0 0 0 0999 V2000
>> 0.5600 -9.3330 -12.4470 C 0 0 0 0 0 0 0 0 0 0 0 0
>> -0.5220 -11.6860 -13.9640 C 0 0 2 0 0 0 0 0 0 0 0 0
>> -1.3890 -10.8900 -13.0130 C 0 0 0 0 0 0 0 0 0 0 0 0
>> -0.9370 -9.5080 -12.5700 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 1.3380 -9.3820 -13.7780 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 0.5150 -9.5890 -15.0480 C 0 0 2 0 0 0 0 0 0 0 0 0
>> 0.0420 -10.9860 -15.1910 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 0.2540 -11.5680 -16.2200 O 0 0 0 0 0 0 0 0 0 0 0 0
>> -0.9330 -12.9740 -14.0030 C 0 0 0 0 0 0 0 0 0 0 0 0
>> -1.2340 -13.7900 -15.1940 C 0 0 0 0 0 0 0 0 0 0 0 0
>> -0.7960 -15.1430 -15.2380 C 0 0 0 0 0 0 0 0 0 0 0 0
>> -1.0610 -15.9350 -16.4000 C 0 0 0 0 0 0 0 0 0 0 0 0
>> -1.7450 -15.3930 -17.5400 C 0 0 0 0 0 0 0 0 0 0 0 0
>> -2.1670 -14.0630 -17.4730 C 0 0 0 0 0 0 0 0 0 0 0 0
>> -1.9260 -13.2750 -16.3360 C 0 0 0 0 0 0 0 0 0 0 0 0
>> -2.0200 -16.1830 -18.7390 C 0 0 0 0 0 0 0 0 0 0 0 0
>> -1.3190 -17.2890 -19.0360 N 0 0 0 0 0 0 0 0 0 0 0 0
>> -2.9740 -15.7940 -19.5590 N 0 0 0 0 0 0 0 0 0 0 0 0
>> 0.8600 -8.8970 -16.1880 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 2.1700 -8.8390 -16.9320 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 2.1750 -8.5140 -18.3280 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 3.3880 -8.4510 -19.0560 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 4.6500 -8.7150 -18.4280 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 4.6430 -9.0360 -17.0580 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 3.4350 -9.0920 -16.3220 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 5.9450 -8.6500 -19.1820 C 0 0 0 0 0 0 0 0 0 0 0 0
>> 6.9230 -9.5390 -18.9420 N 0 0 0 0 0 0 0 0 0 0 0 0
>> 6.1630 -7.7040 -20.1250 N 0 0 0 0 0 0 0 0 0 0 0 0
>> 1 4 1 0
>> 1 5 1 0
>> 2 3 1 0
>> 2 7 1 0
>> 2 9 1 6
>> 3 4 1 0
>> 5 6 1 0
>> 6 7 1 0
>> 6 19 1 6
>> 7 8 2 0
>> 9 10 1 0
>> 10 11 2 0
>> 10 15 1 0
>> 11 12 1 0
>> 12 13 2 0
>> 13 14 1 0
>> 13 16 1 0
>> 14 15 2 0
>> 16 17 2 0
>> 16 18 1 0
>> 19 20 1 0
>> 20 21 2 0
>> 20 25 1 0
>> 21 22 1 0
>> 22 23 2 0
>> 23 24 1 0
>> 23 26 1 0
>> 24 25 2 0
>> 26 27 2 0
>> 26 28 1 0
>> M END
>> """
>>
>> m2 = Chem.MolFromMolBlock(mol)
>>
>> newmol2=Chem.FragmentOnBRICSBonds(m2)
>> frags=Chem.GetMolFrags(newmol2,asMols=True,sanitizeFrags=True)
>> Draw.MolsToGridImage(frags,molsPerRow=4)
>> ##########################################
>>
>> However, some of the fragments are very small. I found that using
>> "BRICS.BRICSDecompose" I can set the minimum size of the fragments with
>> "minFragmentSize". So I tried the following code
>>
>> frag = [Chem.GetMolFrags(x) for x in sorted
>> (BRICS.BRICSDecompose(m2,minFragmentSize=9))]
>>
>>
>> which didn't work, and I got the following error:
>>
>>
>> ###########################################################################
>>
>> ArgumentError Traceback (most recent call last)
>>
>> <ipython-input-35-657d531b48a2> <https://localhost:8080/#> in <module>()
>> ----> 1 frag = [Chem.GetMolFrags(x) for x in
>> sorted(BRICS.BRICSDecompose(m2,minFragmentSize=9))]
>>
>>
>> <ipython-input-35-657d531b48a2> <https://localhost:8080/#> in <listcomp>(.0)
>> ----> 1 frag = [Chem.GetMolFrags(x) for x in
>> sorted(BRICS.BRICSDecompose(m2,minFragmentSize=9))]
>>
>>
>> ArgumentError: Python argument types in
>> rdkit.Chem.rdmolops.GetMolFrags(str)
>> did not match C++ signature:
>>
>> GetMolFrags(RDKit::ROMol mol, bool asMols=False, bool sanitizeFrags=True,
>> boost::python::api::object frags=None, boost::python::api::object
>> fragsMolAtomMapping=None)
>>
>> ###########################################################################
>>
>>
>> I am still learning RDkit (and Python) I am stuck at this. Can someone
>> give me any tips on how to solve this problem or point me in right
>> direction?
>>
>> Best regards,
>>
>> Renato
>>
>> _______________________________________________
>> Rdkit-discuss mailing list
>> [email protected]
>> https://lists.sourceforge.net/lists/listinfo/rdkit-discuss
>>
>
>
> --
> *Rafael da Fonseca Lameiro *
> PhD Student - Medicinal and Biological Chemistry Group (NEQUIMED)
> São Carlos Institute of Chemistry - University of São Paulo - Brazil
> [image: orcid logo 16px] https://orcid.org/0000-0003-4466-2682
>
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