A novel procedure is proposed for 3D-QSAR analysis. The composition of 16 published QSAR datasets has been examined using Quantitative Series Enrichment Analysis (QSEA). The procedure is based on topomer technologies. A heatmap display in combination with topomer CoMFA and a novel series trajectory analysis revealed critical information for the assembly of structures into meaningful series. Global and local centroid structures can be determined from a similarity distance matrix and build the origins for stepwise model building by increasing the similarity radius around the centroid nucleus. The results indicate that the new procedure allows determination of whether compounds belong to an emerging structure-activity relationship and which compounds can be predicted within reliable limits.
Author(s): Bernd Wendt, Richard Cramer