In [118]:
from rdkit import Chem
from rdkit.Chem import AllChem
from rdkit import RDConfig
from rdkit.Chem.Draw import IPythonConsole 
from rdkit.Chem import Draw
from IPython.display import display,Image
import rdkit.Chem.Lipinski as Lipinksy
from rdkit.Chem.Draw import SimilarityMaps



import numpy as np
import pandas as pd

Рисуем ибупрофен:

In [105]:
ibu=Chem.MolFromSmiles('CC(C)CC1=CC=C(C=C1)C(C)C(=O)O')
AllChem.Compute2DCoords(ibu)
display(ibu)

Посчитаем параметры для правила Лепински

In [106]:
def Check_five_lepinsky(molecule):
    if Lipinksy.NumHDonors(molecule) <= 5 and Lipinksy.NumHAcceptors(molecule
        ) <=10 and Lipinksy.rdMolDescriptors.CalcExactMolWt(molecule
        ) < 500 and Lipinksy.rdMolDescriptors.CalcCrippenDescriptors(molecule)[0] <= 5:
        print(molecule)
        return molecule

Способ изменения его SMILES для эмуляции продукта Click Chemistry

In [107]:
ibu_mod = Chem.MolFromSmiles('N1N=NC(=C1)C(C)CC1=CC=C(C=C1)C(C)C(=O)O')
ibu_mod1 = 'N1N=NC(=C1)C(C)CC1=CC=C(C=C1)C(C)C(=O)O'
AllChem.Compute2DCoords(ibu_mod)
display(ibu_mod)

Загрузка азидов и их фильтрация

In [93]:
import pubchempy as pcp
In [109]:
compounds = []
per_page = 10**4
for smiles in ["N=N=N", "NN#N",]:
    for i in range(200):
        try:
            a = pcp.get_properties(
              properties="CanonicalSMILES", 
              identifier=smiles, namespace="smiles", 
              searchtype="substructure",
              RingsNotEmbedded=True,
              listkey_count=per_page, listkey_start=i*per_page
            )
        except:
            print("Page {} returns 500, which is "
                  "our signal to stop.".format(i+1))
            break
        print("Retrieved page {} of {} search".format(i+1, smiles))
        compounds.extend(a)
Retrieved page 1 of N=N=N search
Retrieved page 2 of N=N=N search
Retrieved page 3 of N=N=N search
Retrieved page 4 of N=N=N search
Retrieved page 5 of N=N=N search
Retrieved page 6 of N=N=N search
Retrieved page 7 of N=N=N search
Retrieved page 8 of N=N=N search
Retrieved page 9 of N=N=N search
Retrieved page 10 of N=N=N search
Retrieved page 11 of N=N=N search
Retrieved page 12 of N=N=N search
Retrieved page 13 of N=N=N search
Retrieved page 14 of N=N=N search
Retrieved page 15 of N=N=N search
Retrieved page 16 of N=N=N search
Retrieved page 17 of N=N=N search
Retrieved page 18 of N=N=N search
Page 19 returns 500, which is our signal to stop.
Retrieved page 1 of NN#N search
Page 2 returns 500, which is our signal to stop.
In [110]:
len(compounds)
Out[110]:
176666
In [112]:
compounds = pd.DataFrame(compounds)
compounds.head()
Out[112]:
CID CanonicalSMILES
0 146034876 CCC1C(C2C(C(O1)C)NC(=O)O2)OC3C(C(C(C(O3)C(=O)O...
1 146034848 COC1=CC=C(C=C1)COCC2C(C(C(CO2)N3C(=O)C4=CC=CC=...
2 146034845 COC1=CC=C(C=C1)COCC2C(C(C(C(O2)SC)N=[N+]=[N-])...
3 146034843 CC1CCCC(C1O[Si](C2=CC=CC=C2)(C3=CC=CC=C3)C(C)(...
4 146034841 CC(C)(C)[Si](C1=CC=CC=C1)(C2=CC=CC=C2)OCC3C(C(...
In [113]:
smiles = []

for smile in compounds['CanonicalSMILES']:
    if len(smile) < 30 and not '.' in smile:
        smiles.append(smile)
len(smiles)
Out[113]:
15435
In [115]:
products = []
for smi in smiles:
    if 'N=[N+]=[N-]' in smi:
        newsmi = smi.replace('N=[N+]=[N-]', ibu_mod1)
        
    else:
        continue
        
    try:
        newmol = Chem.MolFromSmiles(newsmi)
        
        if Check_five_lepinsky(newmol):
            products.append(newsmi)
            
    except:
        pass
        
len(products)
<rdkit.Chem.rdchem.Mol object at 0x1081115d0>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x1081115d0>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x1081115d0>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x1081115d0>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x1081115d0>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x1081115d0>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x1081115d0>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x1081115d0>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x1081115d0>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x1081115d0>
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<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
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<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
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<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
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<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
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<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x108111490>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x108111490>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x108111490>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x108111490>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x108111490>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x108111490>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x108111490>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
<rdkit.Chem.rdchem.Mol object at 0x108111490>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
RDKit ERROR: [22:30:13] Explicit valence for atom # 1 Cl, 3, is greater than permitted
<rdkit.Chem.rdchem.Mol object at 0x108111490>
<rdkit.Chem.rdchem.Mol object at 0x11bc09210>
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<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
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<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
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<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
<rdkit.Chem.rdchem.Mol object at 0x1204134e0>
<rdkit.Chem.rdchem.Mol object at 0x1204133f0>
Out[115]:
13887

Иллюстрируем находки

In [116]:
from random import sample

samplelist = []
for item in sample(mass, 9):
    samplelist.append(Chem.MolFromSmiles(item))
Chem.Draw.MolsToGridImage(samplelist,useSVG=True, molsPerRow=3, subImgSize=(300, 300))
Out[116]:
O N N N O OH N N N O HO O O N N N O HO O OH N N N O OH HO N H O O O O N N N O HO N- N+ N P N N N O OH Cl HN O HN N N N O OH O O O N N N O OH O N H N N N O HO

Построим Similiraty Map ибупрофена с пятым веществом из вашего массива.

In [119]:
fp = SimilarityMaps.GetMorganFingerprint(ibu, fpType='bv')
fig, maxweight = SimilarityMaps.GetSimilarityMapForFingerprint(ibu, samplelist[4], 
                                                               SimilarityMaps.GetMorganFingerprint)

3Д структура

In [124]:
m3d=Chem.AddHs(samplelist[4])
Chem.AllChem.EmbedMolecule(m3d)
AllChem.MMFFOptimizeMolecule(m3d,maxIters=300,nonBondedThresh=300)
m3d
Out[124]:
In [125]:
import nglview as nv
nv.show_rdkit(m3d)

ничего

In [ ]: