Simultaneous determination of bioactive conformations and alignment rules by multi-way PLS modeling

In this study, we propose a new three-dimensional quantitative structure-activity relationship (3D-QSAR) method for selecting bioactive conformations and alignment rule simultaneously. The possible conformations of all molecules are generated by conformational analysis and they are superimposed on t...

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Bibliographic Details
Published in:Computational biology and chemistry 2003-07, Vol.27 (3), p.211-216
Main Authors: Hasegawa, Kiyoshi, Arakawa, Masamoto, Funatsu, Kimito
Format: Article
Language:English
Subjects:
3D-QSAR
Algorithms
Alignment rule
benzodiazepine
Benzodiazepines - chemistry
Benzodiazepines - pharmacology
Bioactive conformation
CoMFA
Least-Squares Analysis
Models, Molecular
Models, Theoretical
Molecular Conformation
Molecular Structure
Multi-way PLS
Quantitative Structure-Activity Relationship
Receptor, Cholecystokinin B - antagonists & inhibitors
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Summary:In this study, we propose a new three-dimensional quantitative structure-activity relationship (3D-QSAR) method for selecting bioactive conformations and alignment rule simultaneously. The possible conformations of all molecules are generated by conformational analysis and they are superimposed on template conformer with possible alignment rules. The field variables are calculated as 3D descriptor of structures. Four-way partial least-squares (PLS) analysis is applied, and the conformations and alignment rule largely contributing to biological activity are selected. In order to demonstrate this method, the data set of benzodiazepine derivatives, antagonists of (CCK-B), was used as a test sample. As a result, appropriate conformers and alignment rule were selected and significant PLS model was obtained. The resulting final model could give the reasonable 3D coefficient contour maps. Moreover, external prediction was carried out by use of external data sample and its prediction was proved to be high enough.
ISSN:1476-9271
1476-928X
DOI:10.1016/S0097-8485(02)00055-4