Example Library of Thrombin Inhibitors

22 and 23 show the results of these calculations. The grouping does not depend mainly on the method used. Selective and nonselective COX inhibitors are well separated on the nonlinear map. Hierarchical clustering analyses form a single branch for the selective group of molecules, and also in the visualization of the minimal spanning tree compounds are lined up in the same way. 

The simple NSAID example shows which decisions and parameters influence the result of similarity or diversity examinations. Most important is the choice of the descriptor set which defines the molecular properties considered. The method used for classification and any further computation has only a small effect on the result. 

Topological descriptors can be computed very quickly for a huge number of compounds. These descriptors are able to reproduce the intuitive classification of structural formulas. For this reason, topological descriptors are a good choice to describe the diversity of huge virtual libraries in an automated way. 

Classification based on three-dimensional molecular structures requires more time-consuming computations, but results in more reliable information. These descriptors are able to identify different pharmacological profiles of compounds and thus provide the chemist with novel information that is often not recognizable from the structural formulas directly. 

A published combinatorial library of thrombin inhibitors [133] is examined by means of different computational methods in this section. The library is enumer- 

---