Shape-similarity searching

Andrews KM, Cramer RD. Toward general methods of targeted library design topomer shape similarity searching with diverse structures as queries. / Med Chem 2000 43 1723-40. 

Cramer, R.D., Poss, M.A., Hermsmeier, M.A., Caulfield, T.J., and Kowala, M.C. Prospective identification of biologically active structures by topomer shape similarity searching. /. Med. Chem. 

Docking programs (e.g. DOCK) take the 3D shape of a ligand and a receptor and their complementarity into account. Solely the steric requirements are considered by shape similarity searches (volume-based searching). 

Figure 39 Illustration of size and shape similarity searching...

Size and shape similarity searching complements other types of similarity searching, especially in its ability to locate new classes of substances relative to a particular bioactivity, i.e., not just more examples of the same class. 

There are two classes of volume-based 3D searching. First are the docking programs, which take into account both 3D shape and atomic complementarity and require a receptor site as a query. Second are the volumetric programs, which only account for the steric component some of this class require a receptor site as query, whereas others perform what might be described as a shape similarity search on a small molecule query. 

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