5.1.1 Theory

The Brood distribution includes the program Chomp for fragmenting molecules into databases of potential bioisosteres. Chomp fragments molecules by identifying critical bonds that can be broken. Chomp includes a default set of bond identifiers, or a user can specify a SMARTS file of their own bond identifiers. This file should include a series of SMARTS patterns (1 per line) that each define 2 atoms on opposite ends of the bond to be broken. For example, the SMARTS ``[R]-[!R]'' will cause Chomp to break single bonds between a ring atom and a non-ring atom, while ``[#6]-!@[!#6!#1]'' will cause Chomp to break every single, non-ring bond between a carbon atom and a hetero-atom.

Deletion of these bonds will generate primary fragments. In the ``simple'' mode, only these primary fragments will be written to the database. In the default mode, however, in addition to the primary fragments, all combinations of up to three primary fragments that create a new primary fragment will be generated. In all cases, only fragments with degree ranging from 1 to 4 are written.

The default chemical heuristics seek to break compounds into three types of primary fragments; contiguous ring systems, functional groups, and linkers. Contiguous ring-systems include any set of atoms that are bonded together by at least 1 ring-bond. Thus fused rings and spiro rings are included as a single ring system, but biphenyl is broken into two ring systems. Functional groups are defined as any collection of bonded atoms including one or more hetero-atoms or unsaturated carbons separated by at most a single fully-saturated carbon atom. The linkers are the remaining saturated carbon skeletons. It should be noted that linkers, like functional groups and ring-systems, can be terminal (i.e. degree 1).

				Brood: Fragment replacement for Medicinal Chemistry

				Brood: Fragment replacement for Medicinal Chemistry