ChemSABRE | SABRE | Two-Way R-GroupTable | 2-Way R-Group Table | Structure Activity Relationships | SARvision
Build two-way R-Group tables to analyze Structure Activity Relationships
By Mark Hansen, Ph.D.
A two-way R-Group table highlights key features in R-Group space.
Two-way R-Group tables are a great way to analyze R-Group substitution patterns. R-Group combinations that have not been tried are easily identified while patterns of R-Groups that lead to activity can be highlighted. Two-way tables are slices through an N-dimensional chemical space where each dimension corresponds to one R-Group position in the R-Group table (R1, R2….Rn). In the two-way R-Group tables, R-Group structures from two positions on the scaffold (Rx and Ry) are displayed in the column headers and the row header respectively. Inside each of the table’s cells are a list of the molecules with data that contain these two substation patterns. Ideally, the table is heat-mapped to make active groups of molecules stand out. Using a mouse fly over, individual molecule structures on each row in the cell can be viewed. Two-way R-Group tables can be created for each pair of R-Group positions in the R-Group table. An example is shown below.
There are multiple two-way tables that can be built for a molecule set. Each represents a slice through N-dimensional R-Group space defined by a scaffold core.
To construct a set of two-way R-Group tables: right click on the R-Group tab in the R-Group table in SARvision, and select Exports->SABRE. Inside SABRE, under main menu->R-Groups->Build RxR tables, begin construction of all desired pairwise tables. In the first UI, select the two-way tables to be built by selecting the check-boxes that correspond to the desired R-Group positions. In the second UI, select 1) data to appear inside the table cells, 2) the desired heat-map coloring for the cells, 3) the format for the data and 4) the data that should appear in the mouse fly overs. Note that the two-way R-Group tables can be modified and rebuilt using this Build RxR tables menu option as necessary.
Under the main menu are a series of dialogues that will build custom formatted two-way tables for SAR analysis.
For each two-way R-Group table, there is a filter option on the right of the display. Using this filter, the molecules that populate the table can be filtered in/out of the display to help focus results onto relevant molecules. For example, in the R1 x R2 table below, the filter can be used to select for only molecules to populate the table that have desired R-Group substitutions in R1, R2, R3…Rn positions. Irrelevant or uninteresting substitutions can be removed from analysis using this filter.
The population of molecules in the two-way table can be filtered at any R-position to study only those with R-Groups that are relevant to the current analysis.
Note that under exports these two-way tables can be exported into Excel.