Family structure score

The family characteristics score measures how far the family structure departs from that of a nuclear family. This incorporates questions about marital status of the child s natural parents and present parents/step-parents, whether other people live with the family, including step-children, and whether any children live away from home. 

Structure-based clustering is used to group related compounds for the purpose of HTS data analysis, identification of SAR series, and detection of potential outliers (Engels et al., 2002). In one example, researchers at GNF reported a statistical approach to dynamically score each scaffold family (obtained by prior clustering of screened structures) based on family members HTS activities. This method identifies compounds that share structural similarities and similarly high HTS activities it yielded greatly improved confirmation rates compared to using a static (scaffold-independent) activity cut-off (Yan et al., 2005). 

This entire strategy was applied to each of the four possible scaffold conformations. The top 50 components for each of the scaffold families were merged for each attachment point (i.e. Ri, R2, R3), and hierarchically clustered to maximize the diversity of the compounds chosen for library synthesis. In the end, the 10 best scoring compounds from unique clusters were chosen for each Ri, R2, R3 attachment point. Thus, our final library had the most diverse set of components that fitted our structural hypothesis. 

Naumann and Matter used a set of 26 X-ray structures of eukaryotic protein kinases, which were classified into subfamilies with similar protein-ligand interactions in the ATP binding site. As can be seen in Fig. 3.13, which shows the GPGA score plot, PC 1 separates CDK and MAP/receptor kinases on the left from the family of PKA kinases. The CDK family is represented by two distinct clusters in the target family landscape, formed by two different ATP binding site conformations. They correspond to the activated and inactivated kinase conformations... 

---