Calculate free solvent accessible surface area #RDKit #Chemoinformatics

Recent version of rdkit has method to calculate FreeSASA.
I never used the function so I used it. So I tried to use it.

I calculated freeSASA with very simple molecules Phenol and hydroxy pyridine.

from rdkit import Chem
from rdkit.Chem import rdFreeSASA
from rdkit.Chem.Draw import IPythonConsole
from rdkit.Chem import AllChem
mol1 = Chem.MolFromSmiles('Oc1ccccc1')
mol2 = Chem.MolFromSmiles('Oc1ccncc1')
hmol1 = Chem.AddHs(mol1)
hmol2 = Chem.AddHs(mol2)
AllChem.EmbedMolecule(hmol1)
AllChem.EmbedMolecule(hmol2)

To calculate FreeSASA, prepare raddii is needed.

radii1 = rdFreeSASA.classifyAtoms(hmol1)
radii2 = rdFreeSASA.classifyAtoms(hmol2)

Now ready, let’s calculate FreeSASA.

rdFreeSASA.CalcSASA(hmol1, radii1)
> 137.43293375181904
rdFreeSASA.CalcSASA(hmol2, radii2)
> 128.34398350646256

At first I expected that FreeSASA of pyridine is larger than phenol but result is opposite. So I would like to know details of the reason.

After calculating FreeSASA, each atom has SASA property.

atoms1 = hmol1.GetAtoms()
atoms2 = hmol2.GetAtoms()
for i in range(len(atoms1)):
    print(atoms1[i].GetSymbol(), atoms1[i].GetProp('SASAClassName'), atoms1[i].GetProp("SASA"))
    
sum(float(a.GetProp("SASA")) for a in atoms1)


O Unclassified 10.276248749137361
C Unclassified 5.6117335908330768
C Unclassified 4.8812286399274658
C Unclassified 4.9178986731131236
C Unclassified 4.923259125887407
C Unclassified 4.8241215955112828
C Unclassified 4.8595021375180254
H Unclassified 16.645522512291386
H Unclassified 16.254710140190241
H Unclassified 15.866400115020539
H Unclassified 16.022421230036539
H Unclassified 16.089713316178983
H Unclassified 16.260173926173582
137.43293375181904

for i in range(len(atoms2)):
    print(atoms2[i].GetSymbol(), atoms2[i].GetProp('SASAClassName'), atoms2[i].GetProp("SASA"))
    
sum(float(a.GetProp("SASA")) for a in atoms2)

O Unclassified 10.443721296042458
C Unclassified 5.5711494477882848
C Unclassified 4.7609239637426501
C Unclassified 4.9640112698257193
N Unclassified 11.64593971756287
C Unclassified 4.6638358234073181
C Unclassified 5.0220733873889731
H Unclassified 16.474508728534751
H Unclassified 16.091035411384464
H Unclassified 16.409635462176684
H Unclassified 16.194368688350266
H Unclassified 16.102780310258137
128.34398350646256

The reason is that phenol has one more hydrogen atom and it occupy more surface area than aromatic nitrogen.

I think the parameter can use a property for GCN.
Today’s sample code is here.

Published by iwatobipen

I'm medicinal chemist in mid size of pharmaceutical company. I love chemoinfo, cording, organic synthesis, my family.

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