To extend chemistry handling capabilities of Plexus Connect, the R-group decomposition feature has been added in version 20.20.0. As functional groups have significant impact to physical-chemical properties of a molecule, their visualization helps better understand structure-activity relationships between molecules in a given dataset. Using R-group decomposition, structural variations of molecules can be displayed in a comprehensible plot, different functional groups can be compared and relationships between molecules and their properties can easily be explored.
Based on the current implementation in Plexus Connect, the R-group decomposition can be performed for a given collection of molecules which consist of R1 and R2 groups and a scaffold. The scaffold is defined by the user and usually represents the central structure of the molecule. By performing R-group decomposition, the molecules are queried against the scaffold, and its ligands (attachment groups) at certain positions are identified. The ligand attachment points are represented by R-groups. As a result of decomposition, variations of ligands present in the queried molecules are displayed as values on axes (by default, R1 groups as horizontal axis values and R2 groups as vertical axis values).
There are two types of visualization of the R-group decomposition plot:
To perform R-group decomposition in your dataset, open the corresponding view (grid view or form view) containing your structures and click the R-group icon on the navigation toolbar ( ).
Using the toggle button at the top of the "Add new R-group decomposition" dialog window, you can display the R-group decomposition results as a table (toggle on ) or as a scatterplot (toggle off ).
Below this option, the scaffold and the R1 and R2 groups need to be defined. Please note: to execute the R-group decomposition, exactly two R-groups (R1 and R2) must be defined. Defining a single R-group or more than two R-groups is not supported. To draw the desired structure, click the pen icon and draw your scaffold with R-groups in Marvin JS. In your dataset, Plexus Connect will perform substructure search against your scaffold. Its ligands in R1 and R2 positions will be displayed as an R-group decomposition plot.
The options available for field selection depend on the selected R-group decomposition plot type – table or scatterplot.
In the case of an R-group table , a cell value field needs to be selected. From the dropdown menu, select the field whose values are to be displayed in the cells of the R-group table. The values will be colored based on the current color scheme displayed next to the field selection dropdown. To customize the color scheme, set the desired colors for maximum and minimum values from a color palette that opens by clicking the corresponding color field.
When displaying an R-group decomposition plot as a scatterplot (toggle button "Display as a table" off), coloring, size, and shape of datapoints need to be set using field selection from the appropriate dropdown menus. Custom coloring of datapoints is also available – the color scheme is customizable, in a similar way as cell value color customization for R-group table (see above).
Apart from the field selection described above, the properties to be displayed in the Card can be selected by clicking the corresponding fields in the Additional fields section (below the cell value field dropdown in R-group tables and below datapoint color/size/shape dropdowns in R-group scatterplots). Displaying a structure and relevant properties on the Card can be helpful to discover your molecules and their characteristics in the context of other molecules visualized in the same R-group decomposition plot. By hovering over a cell (in an R-group table) or over a data point (in an R-group scatterplot), the structure and selected properties of the related molecule appear on the Card.
Both for R-groups table and scatterplots, variations of ligands are shown as values on the axes: R1 groups on the horizontal axis and R2 groups on the vertical axis. To define a region for displaying data, the R-group plot can be zoomed in and out using the mouse wheel (this functionality is available for R-group scatterplots only).
The single axis zoom tool (represented by blue lines along each axis) provides additional navigation functionality. In both tables and scatterplots, moving one of the blue lines is used for scrolling. In scatterplots, changing the size of the blue lines by dragging one of their anchor points will zoom in/out the scatterplot along the given axis.
The scrollable legend panel of cell value coloring (for R-group tables) and data point coloring (for R-group scatterplots) shows the values of the selected database field (e.g. Calculated MolWeight) and their corresponding colors. You can switch to a new field by clicking the field name, which opens a list of all available fields. In the case of R-group scatterplots, the data point size and shape are also shown in the corresponding legend panels.
The R-group decomposition result set (i.e. molecules containing the scaffold and the R1 and R2 groups) can be stored in the form of a list by clicking the Lists icon on the upper control panel and choosing New List from the selection option. More details about creating lists and lists management are available in the Plexus Connect documentation here.
As Plexus Connect enables data sharing between collaborators via URL, the result set of the R-group decomposition can also be shared. The URL reflects the R-group decomposition result set, the scaffold with R-groups and the R-group plot. By sharing the URL, your peers can access the result set and further explore your R-group decomposition results. Detailed guidelines about sharing views via URL can be found here.
Similarly as in Plexus Connect Charts, data displayed in an R-group decomposition plot are automatically synchronized with a corresponding view. This means that data selected in the R-group decomposition plot (both table and scatterplot) is also selected in the view and vice versa. The structures in the view are aligned based on scaffold and R-groups orientation defined by the user. The scaffold and the R-groups are colored differently, helping to visually distinguish between the scaffold and the R-groups.
Data selection can be done either within the view or within the R-group plot using one of the available selection tools:
Cherry-picking (selection of individual datapoints in a scatterplot or individual cells in a table)
The selection tools for rectangular selection and deselection, freehand selection and deselection can be found in the dropdown menu on the legend panel.
By clicking the Deselect All icon on the legend panel, the whole selection switches back to its default state both in the view and in the R-group plot.
The R-group decomposition plot can be saved as a PNG or SVG file. This functionality is available by clicking the menu option on the legend panel.
R-group decomposition and related functionalities can be enabled / disabled by Plexus Connect administrator using PLEXUS_CHARTS business flag available in the featureFlags.properties file by setting the property to true or false, respectively. The changes will take effect the next log-in to Plexus Connect.