Pharmacophoric Fingerprint Method (TOPP) for 3D-QSAR Modeling: Application to CYP2D6 Metabolic Stability

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• 作者：Simone Sciabola ; Iñ ; aki Morao ; Marcel J. de Groot
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2007
• 出版时间：January 2007
• 年：2007
• 卷：47
• 期：1
• 页码：76 - 84
• 全文大小：186K
• 年卷期：v.47,no.1(January 2007)
• ISSN：1549-960X

文摘

The application of a new 3-point pharmacophore-fingerprinting package (TOPP, Triplets Of PharmacophoricPoints) to develop QSAR models is discussed. In the CYP2D6 metabolic stability case, these 3Dpharmacophoric fingerprints have shown to be as valid as other 3D descriptors and 2D features. Interestingly,it was found in the 3D models that the use of more realistic substrate conformations, by an additionaldocking step, did not improve the statistical results significantly. A detailed analysis of the generatedpharmacophoric hypotheses is consistent with the previously proposed dual interaction mode of substrateswithin the active site of CYP2D6.