Molecular Fragments and Fingerprints - Design and Use of Relational Databases in Chemistry - page 98

Another useful fragment-based function computes the polar surface area
of a molecule using the method described by Ertl, Rohde, and Selzer. 7 The
SMARTS and partial surface areas for the fragments described by Ertl are
shown in Table A.3 in the Appendix. That table is created as

Create Table tpsa (psa Numeric, smarts Text, description Text);

The following function computes the tpsa value using the tpsa table.

Create Function gnova.tpsa(text)
Returns Numeric As $EOSQL$
Select sum(psa*count_matches($1,smarts)) From tpsa;
$EOSQL$ Language SQL;

This function could be used to add a column of tpsa to any table contain-
ing SMILES.
There are other fragment-based methods 8,9 published that could be
implemented using the approach described here. As long as the fragments
can be defined using SMARTS and the molecular property is a simple sum
(or product or other aggregate function), a relational table of fragment values
can be used. Using the match or count _ matches functions from Chapter
7, an SQL function can be easily written to compute the property value.

References

1. Durant, J.L., Leland, B.A., Henry, D.R., and Nourse, J.G., 2002. Reoptimization
of MDL keys for use in drug discovery, J. Chem. Inf. Comput. Sci., 42(6):
1273-1280.

2. Hash function. 2008. http://en.wikipedia.org/wiki/Hash_function

(accessed April 18, 2008).

3. Fingerprints—Screening and Similarity. 2007. http://daylight.com/
dayhtml/doc/theory.finger.html (accessed April 18, 2008).

4. Bender, A., Mussa, H.Y., Glen, R.C., and Reiling, S. 2004. Molecular similar-
ity searching using atom environments, information-based feature selection,
and a naive Bayesian classifier. J. Chem. Inf. Comput. Sci. 44(1):170-178.

5. Tanimoto, T.T. 1957. IBM Internal Report, November 17.

6. Hert, J., Willett, P., Wilton, D.J., Acklin, P., Azzaoui, K., Jacoby, E., and
Schuffenhauer, A. 2004. Comparison of fingerprint-based methods for virtual
screening using multiple bioactive reference structures. J. Chem. Inf. Comput.
Sci. 44(3):1177-1185.

7. Ertl, P., Rohde, B., and Selzer, P. 2000. Fast calculation of molecular polar
surface area as a sum of fragment-based contributions and its application to
the prediction of drug transport properties. J. Med. Chem . 43:3714-3717.

8. Wildman, S.A. and Crippen, G.M. 1999. Prediction of physicochemical
parameters by atomic contributions. J. Chem. Inf. Comput. Sci . 39: 868-873.

9. Andrews R., Craik, D.J., and Martin, J.L. 1984. Functional group contribu-
tions to drug-receptor interactions. J. Med. Chem . 27(12): 1648-1657.