Beneficial transforms that could solve a drug discovery problem may not be connected to any exact structure that a user might query. With Matcher, a broader net can be cast with substructure searches for transforms of interest. When a query takes the form of one substructure transforming to another substructure, the resulting transforms can relate many fragments to many other fragments, a situation that we define as a 'many-to-many' query (Figure ). Matcher can group 'many-to-many' transforms by fragment for concise visualization of how each fragment compares to others. This workflow makes it easy to find fragments with a defined substructure that are 'privileged' for a property of interest, or in other words, fragments that are global maxima (or minima) within their local structure/property space. This query will find all MMPs where the nitrogen-containing portion of an amide changes. The maximum number of heavy atoms in the variable fragments is limited to 8 atoms using 'advanced options'. b) The found transforms are grouped by 'TO' fragment, i.e. the right-hand side of each transform. The transform clusters are sorted in descending order of percentage of transforms resulting in median increase in hERG IC50, and filtered to only show clusters with >4 transforms. As an example, the first row in the table shows that there are 17 transforms involving various amino fragments (right-most column) being transformed to morpholino, and 94% of these transforms exhibit a median increase in hERG IC50. c) Plot of all MMPs for the selected row in the transform table, with structures of selected MMP points displayed.