A recent post on In the Pipeline talked about a recent JACS communication on the total synthesis of the natural product maoecrystal V. The article is open access:
http://pubs.acs.org/doi/abs/10.1021/jacs.6b06623
Here's the ToC figure, which shows a sketch of the final product on the left:
Since I've been looking at how well the RDKit does at conformation generation for highly constrained systems, I thought this would be a nice example molecule to try out. I was also quite curious about the shape of that beast.
The first problem was getting the structure in. I wasn't completely confident in my ability to reproduce that sketch and JACS, of course, doesn't have a way to provide structures in electronic form. Fortunately the authors had solved x-ray structures of their final product and a bunch of intermediates and the CIF files were in the supplementary material. So I converted the CIF to a mol file with OpenBabel (hopefully using the correct CIF file... they aren't particularly well labelled as far as I can tell) and got started from there.
Note: I haven't been able to make blogger work well with py3Dmol, so there are static screenshots below of the 3D structures. Interactive structures are available by viewing the original notebook: https://github.com/greglandrum/rdkit_blog/blob/master/notebooks/3D%20structure%20of%20a%20natural%20product.ipynb with the fantastic nbviewer: http://nbviewer.jupyter.org/github/greglandrum/rdkit_blog/blob/master/notebooks/3D%20structure%20of%20a%20natural%20product.ipynb
Here's the ToC figure, which shows a sketch of the final product on the left:
Since I've been looking at how well the RDKit does at conformation generation for highly constrained systems, I thought this would be a nice example molecule to try out. I was also quite curious about the shape of that beast.
The first problem was getting the structure in. I wasn't completely confident in my ability to reproduce that sketch and JACS, of course, doesn't have a way to provide structures in electronic form. Fortunately the authors had solved x-ray structures of their final product and a bunch of intermediates and the CIF files were in the supplementary material. So I converted the CIF to a mol file with OpenBabel (hopefully using the correct CIF file... they aren't particularly well labelled as far as I can tell) and got started from there.
Note: I haven't been able to make blogger work well with py3Dmol, so there are static screenshots below of the 3D structures. Interactive structures are available by viewing the original notebook: https://github.com/greglandrum/rdkit_blog/blob/master/notebooks/3D%20structure%20of%20a%20natural%20product.ipynb with the fantastic nbviewer: http://nbviewer.jupyter.org/github/greglandrum/rdkit_blog/blob/master/notebooks/3D%20structure%20of%20a%20natural%20product.ipynb
In [1]:
from rdkit import Chem
from rdkit.Chem import AllChem
from rdkit.Chem import Draw
from rdkit.Chem.Draw import IPythonConsole
from rdkit import rdBase
print(rdBase.rdkitVersion)
import os,time
print( time.asctime())
We'll use py3Dmol to show structures in the notebook
In [5]:
import py3Dmol
def drawit(m,p=None,confId=-1):
mb = Chem.MolToMolBlock(m,confId=confId)
if p is None:
p = py3Dmol.view(width=400,height=400)
p.removeAllModels()
p.addModel(mb,'sdf')
p.setStyle({'stick':{}})
p.setBackgroundColor('0xeeeeee')
p.zoomTo()
return p.show()
Start by reading in the mol file and displaying that:
In [8]:
mExpt = Chem.MolFromMolFile("/home/glandrum/Downloads/paper/ja6b06623_si_010.cif.mol",removeHs=False)
drawit(mExpt)
Out[8]:
Now generate a conformer for the molecule:
In [14]:
m = Chem.MolFromMolFile("/home/glandrum/Downloads/paper/ja6b06623_si_010.cif.mol",removeHs=False)
Chem.AssignAtomChiralTagsFromStructure(m)
AllChem.EmbedMolecule(m,useExpTorsionAnglePrefs=True,useBasicKnowledge=True)
drawit(m)
Out[14]:
At least by eye that looks very close, let's check the RMS:
In [20]:
print("RMS: ",AllChem.GetBestRMS(m,mExpt),
"Heavy Atom RMS:",
AllChem.GetBestRMS(Chem.RemoveHs(m),Chem.RemoveHs(mExpt)))
Not bad! But then, this is a highly constrained structure.
Because we can, let's look at the two structures superimposed:
Because we can, let's look at the two structures superimposed:
In [21]:
AllChem.AlignMol(m,mExpt)
mb = Chem.MolToMolBlock(m)
mbExpt = Chem.MolToMolBlock(mExpt)
p = py3Dmol.view(width=400,height=400)
p.removeAllModels()
p.addModel(mb,'sdf')
p.addModel(mbExpt,'sdf')
p.setStyle({'stick':{}})
p.setBackgroundColor('0xeeeeee')
p.zoomTo()
p.show()
Out[21]:
Finally, a bit of 2D work.
Just to have it, here's the SMILES for maoecrystal V
In [12]:
Chem.MolToSmiles(Chem.RemoveHs(m),True)
Out[12]:
Let's see how well the RDKit's 2D coordinate generation works here:
In [13]:
Chem.MolFromSmiles('C[C@H]1C(=O)[C@@]23CC[C@@H]1C[C@@]21O[C@@H]2C(C)(C)C=CC(=O)[C@]23COC1=O')
Out[13]:
Not great, but definitely not as bad as I had expected.
In [ ]:
