Structure-activity landscape index

Activity cliff, Structure-activity similarity maps, Structure-activity landscape index, Structure-activity... 

Structure-activity similarity (SAS) maps, first described by Shanmugasundaram and Maggiora (35), are pairwise plots of the structure similarity against the activity similarity. The resultant plot can be divided into four quadrants, allowing one to identify molecules characteristic of one of four possible behaviors smooth regions of the SAR space (rough), activity cliffs, nondescript (i.e., low structural similarity and low activity similarity), and scaffold hops (low structural similarity but high activity similarity). Recently, SAS maps have been extended to take into account multiple descriptor representations (two and three dimensions) (36, 37). In addition to SAS maps, other pairwise metrics to characterize and visualize SAR landscapes have been developed such as the structure-activity landscape index (SALI) (38) and the structure-activity index (SARI) (39). 

Guha R, Van Drie JH (2008) The structure-activity landscape index identifying and quantifying activity-cliffs. J Chem Inf Model 48(3) 646-658... 

Structure-Activity Landscape Index = SAL Index Stmcture/Response Correlations... 

A quantification of the concept of presence of activity cliffs was proposed in terms of the SAL Index (or Structure-Activity Landscape Index), which for a pair of compounds is defined as [Maggiora, 2006 Guha and Ven Drie, 2008]... 

Guha, R. and Ven Drie, J.H. (2008) Structure-activity landscape index identifying and quantifying activity difFs. /. Chem. Inf. Model, 48, 646—658. 

The introduction of a structure-activity landscape index (SALI), as proposed by Guha and Van Drie [51], helps to identify and quantify activity cliffs. This SALI is defined as follows ... 

Guha> R.> Van Drie> J. H. (2008a). Structure-activity landscape index Identifying and quantifying activity cliffs. The Journal of Chemical Information and Modeling, 48, 646. 

SAR Index. The SAR Index (SARI) has recently been introduced to quantitatively capture the continuous, discontinuous, or heterogeneous nature of activity landscapes and SARs. Similar to SAS maps, it exclusively relies on the 2D structural similarity and potency distribution within a set of active compounds. However, SARI aims to categorize the SARs of a population of compound sets without employing idealized reference states. It generates a numerical index between 0 and 1 that reflects the (dis-)continuity of the SARs under consideration. SARI distinguishes between three major categories of... 

The SAR index (SARI) provides a composite score of individual SAR continuity and discontinuity functions, which have been introduced by Peltason et al. [83,47]. However, in order to identify activity cliffs, local scoring functions focusing directly on SAR discontinuity in a local environment around a chemical structure of interest are more informative than global activity landscape overviews. Regions of SAR discontinuity provide a lot of information on the SAR of a particular chemical series for deriving a pharmacophore hypothesis. For this case, the compound discontinuity score was introduced [80]. This variation of the SARI formalism is aiming to quantify individual molecular contributions to local SAR discontinuity. Typically, the... 

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