Organic Molecule generated from SMILES

In the following examples we will be generating conformations of the quinine molecule.

SMILES
COC1=CC2=C(C=CN=C2C=C1)[C@H]([C@@H]3C[C@@H]4CCN3C[C@@H]4C=C)O

Conformer Generation

We start by importing the packages

from pathlib import Path
from aqme.csearch import csearch

Then we define where will the documents be created, in this case we want to create a new folder named 'quinine_folder' in the same folder that we are.

w_dir_main = Path.cwd()
sdf_path = w_dir_main/'quinine_folder'

Finally we proceed to the conformational search using the smiles string of the molecule.

smiles = 'COC1=CC2=C(C=CN=C2C=C1)[C@H]([C@@H]3C[C@@H]4CCN3C[C@@H]4C=C)O'
csearch(destination=sdf_path,
        smi=smiles,
        name='quinine',
        program='rdkit')

Here we are specifying that we want to use rdkit for the conformer generation when we specify program='rdkit' and we are specifying the base name of the output files to be 'quinine'.

At this point we will have a new folder already created named 'quinine_folder' that contains a file named quinine_rdkit.sdf that contains all the conformers generated.

If we wanted to use fullmonte instead to generate the geometries then we just need to change the program parameter to 'fullmonte':

smiles = 'COC1=CC2=C(C=CN=C2C=C1)[C@H]([C@@H]3C[C@@H]4CCN3C[C@@H]4C=C)O'
csearch(destination=sdf_path,
        smi=smiles,
        name='quinine',
        program='fullmonte')

Minimizing the conformations

Back to our conformers generated using rdkit we might be interested in running an energy minization using XTB or ANI. To do so we will need the CMIN module.

from aqme.cmin import cmin

After importing the module we just need to provide the files that we have generated. In this case we already know that we have a single file so we can directly provide its location to the CMIN module.

sdf_cmin_path = w_dir_main/'quinine_ani'
sdf_files = [str(sdf_path/'quinine_rdkit.sdf'),]
cmin(destination=sdf_cmin_path,
     files=sdf_files,
     program='ani')

Here 'destination' is the folder where the new optimized geometries will be generated, 'files' is a list of files that we want to minimize and 'program' is specifying that we want to run the minimizations using 'ani'.

If we do not know the exact name of the file or have several files we can get the list of all the files with the following line.

sdf_files = sdf_path.glob('*.sdf')

Using csv files as input

Another way of providing the molecule to the program is by writing it into a csv file. Lets asume we have in our working directory the file 'ML_test.csv' with the following contents:

code_name,SMILES
quinine,COC1=CC2=C(C=CN=C2C=C1)[C@H]([C@@H]3C[C@@H]4CCN3C[C@@H]4C=C)O

With this file we can run the same conformer search that we run at the beggining with the following code:

from pathlib import Path
from aqme.csearch import csearch

w_dir_main = Path.cwd()
sdf_path = w_dir_main/'quinine_folder'
csv_input = w_dir_main/'ML_test.csv'

csearch(destination=sdf_path,
        program='rdkit',
        input=csv_input)

Using csv files allows specifying multiple molecules by their SMILES string in a single file and facilitates the reusability of the code. If we change the contents of 'ML_test.csv' to:

code_name,SMILES
methane,C
ethane,CC
propane,CCC
butane,CCCC
pentane,CCCCC

We can re-run the exact same code, and we will end with the conformers of each one of these molecules in the same directory. If we want to have them in a different folder we can simply change the destination:

csearch(destination='alkanes_folder',
        program='rdkit',
        input=csv_input)