Cheminformatics toolkit face-off - LogP and TPSA

Updated 23/04/08 (see below)

In a recent post, I discussed some thoughts I had about using the Pybel API as a generic API for cheminformatics toolkits. I've started to implement this (more on this at a later date) and have begun writing some tests to compare results from different toolkits. To begin with, I was hoping that RDKit (Jan2008), CDK (1.0.2) and OpenBabel (dev, soon-to-be 2.2.0) could agree on LogP and TPSA values calculated with the same group contribution approach.

The code is below, but first here are the results:

ALogP
=====
****Example1*****
The calculated value from JCICS, 1999, 39, 868 is 1.400000
cinfony.rdk {'MolLogP': 1.4007999999999998,
'pyMolLogP': 1.4007999999999998}
cinfony.pybel {'LogP': 0.80749999999999988}



****Example2*****
The calculated value from JCICS, 1999, 39, 868 is 2.750000
cinfony.rdk {'MolLogP': 2.7486000000000006,
'pyMolLogP': 2.7486000000000006}
cinfony.pybel {'LogP': 1.6415999999999995}



****methane*****
The calculated value from JCICS, 1999, 39, 868 is 0.144100
cinfony.rdk {'MolLogP': 0.6331, 'pyMolLogP': 0.6331}
cinfony.pybel {'LogP': 0.14410000000000001}



TPSA
====
****metoprolol*****
The calculated value from JMC, 2000, 43, 3714 is 50.700000
cinfony.cdk {'tpsa': 50.719999999999999}
cinfony.rdk {'TPSA': 50.719999999999999}
cinfony.pybel {'TPSA': 50.719999999999999}



****nordiazempam*****
The calculated value from JMC, 2000, 43, 3714 is 41.500000
cinfony.cdk {'tpsa': 41.460000000000001}
cinfony.rdk {'TPSA': 41.460000000000001}
cinfony.pybel {'TPSA': 41.460000000000001}

The good news is that they all agree on the TPSA of the two examples. The bad news is that CDK 1.0.2 does not calculate ALogP, and OpenBabel doesn't seem to be doing well for the more complicated examples (which are taken from the JCICS paper). It's possible that OpenBabel is using a different parameterisation than the paper I reference. I'm not sure either if there's any difference between the two ALogP values that RDKit calculates. Hopefully, the people that know will comment below.

Update (23/04/08): (1) I calculated the LogP of methane incorrectly - it should be 0.63610. (2) RDKit has a transposition error in the value for C in methane (only a minor error). (3) OpenBabel calculates the correct answer if hydrogens are added. I'm going to recommend that the descriptor adds the hydrogens itself, to avoid user errors in future. (Done! Thanks to Chris Morley.) (4) The two ALogP descriptors in RDKit are implementations in two different languages, one in C++, the other in Python. They should be identical. (Thanks to Greg Landrum of RDKit for identifying several of these issues)

Here's the code...

from cinfony import cdk, rdk, pybel


descs = [("ALogP", "JCICS, 1999, 39, 868"),
("TPSA", "JMC, 2000, 43, 3714")]
toolkits = [(cdk, {'ALogP': None, 'TPSA': ['tpsa']}),
(rdk, {'ALogP': ['MolLogP', 'pyMolLogP'],
'TPSA': ['TPSA']}),
(pybel, {'ALogP': ['LogP'], 'TPSA': ['TPSA']})]
testcases = {'ALogP':
{"methane": (0.1441, 'C'),
"Example1": (1.40, 'c1(O)ccccc1(OC)'),
"Example2": (2.75, 'c1ccccc1c1ccccn1')},
'TPSA':
{"metoprolol": (50.7,
"c1(OCC(O)CNC(C)C)ccc(CCOC)cc1"),
"nordiazempam": (41.5,
"c1c(Cl)ccc2NC(=O)CN=C(c3ccccc3)c12")}}

for desc, ref in descs:
print desc + "\n" + "="*len(desc)
for k, v in testcases[desc].iteritems():
print "****%s*****" % k
print "The calculated value from %s is %f" % (ref, v[0])
for toolkit in toolkits:
if toolkit[1][desc]:
mol = toolkit[0].readstring("smi", v[1])
print toolkit[0].__name__,
print mol.calcdesc(toolkit[1][desc])
print "\n\n"

Image credit: pfly