Clustering files of chemical structures using the Székely–Rizzo generalization of Ward's method

Ward's method is extensively used for clustering chemical structures represented by 2D fingerprints. This paper compares Ward clusterings of 14 datasets (containing between 278 and 4332 molecules) with those obtained using the Székely–Rizzo clustering method, a generalization of Ward's method. The clusters resulting from these two methods were evaluated by the extent to which the various classifications were able to group active molecules together, using a novel criterion of clustering effectiveness. Analysis of a total of 1400 classifications (Ward and Székely–Rizzo clustering methods, 14 different datasets, 5 different fingerprints and 10 different distance coefficients) demonstrated the general superiority of the Székely–Rizzo method. The distance coefficient first described by Soergel performed extremely well in these experiments, and this was also the case when it was used in simulated virtual screening experiments.