Computer-aided drug design (CADD) has been credited to the modern patterns in compound characterization in drug discovery following its inception in 1981 [43]. It represents an advancement when compared to HTS as it requires minimal compound design or prior knowledge, but can yield multiple hit compounds among which promising candidates have been elected. The typical role of CADD in drug discovery is to screen out large compound libraries into smaller clusters of predicted active compounds (Figure 5.1), enabling optimization of lead compounds by improving the biological properties (like affinity and ADMET) and building chemotypes from a nucleating site by combining fragments with optimized function.Clustering has been applied as a means to select representatives from screening libraries [44]. Screening hits include molecules that specifically bind to the target in addition to a greater number of nonspecific compounds requiring a triaging process to filter these out (Figure 5.1). Thus, such a large library that contains a number of possible hits is further downsized and clustered into series.