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:
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
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
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
import pubchempy as pcp
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.
len(compounds)
176666
compounds = pd.DataFrame(compounds)
compounds.head()
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(... |
smiles = []
for smile in compounds['CanonicalSMILES']:
if len(smile) < 30 and not '.' in smile:
smiles.append(smile)
len(smiles)
15435
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)
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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
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RDKit ERROR: [22:30:20] Explicit valence for atom # 4 Cl, 3, is greater than permitted
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RDKit ERROR: [22:30:33] Explicit valence for atom # 25 Cl, 3, is greater than permitted
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13887
Иллюстрируем находки
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))
Построим Similiraty Map ибупрофена с пятым веществом из вашего массива.
fp = SimilarityMaps.GetMorganFingerprint(ibu, fpType='bv')
fig, maxweight = SimilarityMaps.GetSimilarityMapForFingerprint(ibu, samplelist[4],
SimilarityMaps.GetMorganFingerprint)
3Д структура
m3d=Chem.AddHs(samplelist[4])
Chem.AllChem.EmbedMolecule(m3d)
AllChem.MMFFOptimizeMolecule(m3d,maxIters=300,nonBondedThresh=300)
m3d
import nglview as nv
nv.show_rdkit(m3d)
ничего