Fig. 1.

Illustration of the basic idea of the Knowledge-Guided Scoring (KGS) method. The sea represents the hypothetical “protein-ligand interaction space”. A given query complex (Q) is a small island somewhere in the sea. Binding affinity prediction by current scoring functions, most of which are additive models, is to sail from the origin of this space (at the lower-left corner) to the destination (Q). By the KGS method, if a reference complex (R) resembling the query complex can be found first, one can sail from the R island to the Q island for instead, which is assumed to be a less difficult journey