ci060143q_si_001.doc (389.5 kB)
Download filePharmacophoric Fingerprint Method (TOPP) for 3D-QSAR Modeling: Application to CYP2D6 Metabolic Stability
journal contribution
posted on 22.01.2007, 00:00 authored by Simone Sciabola, Iñaki Morao, Marcel J. de GrootThe application of a new 3-point pharmacophore-fingerprinting package (TOPP, Triplets Of Pharmacophoric
Points) to develop QSAR models is discussed. In the CYP2D6 metabolic stability case, these 3D
pharmacophoric 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 additional
docking step, did not improve the statistical results significantly. A detailed analysis of the generated
pharmacophoric hypotheses is consistent with the previously proposed dual interaction mode of substrates
within the active site of CYP2D6.