Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1021/ci900313u
Titel (primär) Chemical domain of QSAR models from atom-centered fragments
Autor Kühne, R. ORCID logo ; Ebert, R.-U.; Schüürmann, G.
Quelle Journal of Chemical Information and Modeling
Erscheinungsjahr 2009
Department OEC
Band/Volume 49
Heft 12
Seite von 2660
Seite bis 2669
Sprache englisch
Abstract A methodology to characterize the chemical domain Of qualitative and quantitative structure-activity relationship (QSAR) models based oil the atom-centered fragment (ACF) approach is introduced. ACFs decompose the molecule into structural pieces, with each non-hydrogen atom of the molecule acting as an ACF center. ACFs vary with respect to their size in terms of the path length covered in each bonding direction starting from a given central atom and how comprehensively the neighbor atoms (including hydrogen) are described in terms of element type and bonding environment. In addition to these different levels of ACF definitions, the ACF match mode as degree of strictness of the ACF comparison between a test compound and a given ACF pool (such as from a training set) has to be specified. Analyses of the prediction statistics Of three QSAR models with their training sets as well as with external test sets and associated Subsets demonstrate a clear relationship between the prediction performance and the levels of ACF definition and match mode. The findings suggest that second-order ACFs combined with a borderline match mode may serve as a generic and at the same time a mechanistically sound tool to define and evaluate the chemical domain of QSAR models. Moreover, four standard categories of the ACF-based membership to a given chemical domain (outside, borderline outside, borderline inside, inside) are introduced that provide more specific information about the expected QSAR prediction performance. As such, the ACF-based characterization of the chemical domain appears to be particularly useful for QSAR applications in the context of REACH and other regulatory schemes addressing the safety evaluation of chemical compounds
dauerhafte UFZ-Verlinkung
Kühne, R., Ebert, R.-U., Schüürmann, G. (2009):
Chemical domain of QSAR models from atom-centered fragments
J. Chem Inf. Model. 49 (12), 2660 - 2669 10.1021/ci900313u