title: Nearly no Scoring Function Without a Hansch-Analysis.
abstract: Corwin Hansch is well-known as the father, inventor, and promoter of quantitative structure-activity relationships. Usually, QSAR is seen as a ligand-based design method correlating molecular structure or property descriptors to biological activity. QSAR is seldom mentioned in relation to structure-based approaches, although it is the centerpiece of nearly every empirical scoring function. QSAR techniques are applied on various levels, from the fitting of scoring terms to biological affinity data in empirical scoring functions up to the fine-tuning of individual aspects of protein-ligand interactions. In the following, we report on current findings for our scoring approach HYDE, which are based upon both the idea of QSAR and Hansch's historical logP data. We relate the molecular surface area of 594 diverse compounds to their experimental octanol/water partition coefficients aiming at new insights in hydrogen bonding and dehydration energies of solutes. Donors and acceptors which are far from each other contribute with nearly constant increments to the logP value. The solubility in the aqueous phase is however not increased with the number of hydrogen bonds a polar group is able to form. Although signs are found that these facts have been known for many years, they have implications for modern scoring function design.
authors.affiliation: Center for Bioinformatics, University of Hamburg, Bundesstr. 43, 20146 Hamburg, Germany phone/fax: 0049 40 42838 7350.
authors.forename: Nadine
authors.initials: N
authors.lastname: Schneider
authors.affiliation: Bayer CropScience AG, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Klein
authors.affiliation: Bayer CropScience AG, Industriepark Hoechst, 65926 Frankfurt am Main, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Lange
authors.affiliation: Center for Bioinformatics, University of Hamburg, Bundesstr. 43, 20146 Hamburg, Germany phone/fax: 0049 40 42838 7350. rarey@zbh.uni-hamburg.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rarey
keywords: HYDE; Molecular surface; QSAR; Scoring; logP