an optimized compound is derived from a reference compound by replacing its core , or central portion , with a new core . criteria for accepting a candidate replacement core include said candidate replacement core &# 39 ; s ability to connect to the side chains of the reference compound in a chemically reasonable geometry that closely approximates the geometry which said side chains exhibited in the reference compound . the replacement core that substitutes for the core of a reference compound may be extended by linker groups , if said extension improves the achievable alignment of attachment bonds with those of the reference compound over the alignment that could be achieved without the use of linkers . this is done in a single stage , without a combinatorial testing of the number of linkers to be used in the various attachment bonds .