Topological similarity searching

Sheridan, R.P., Singh, S.B., Fluder, E.M., and Kearsley, S.K. (2001) Protocols for bridging the peptide to nonpeptide gap in topological similarity searches./ourraoi of Chemical Information and Computer Sciences, 41, 1395-1406. 

Figure 35 Top-ranked retrieval from a near-neighbor browse topological similarity search for alendronate (66376-36-1)...

Figure 38 Top-ranked retrieval from topological similarity search for a set of known anticonvulsants...

CAS has developed a molecular property similarity search capability that will allow the rapid scanning of millions of substances with good precision. The technique can be combined with other techniques such as topological similarity searching to provide more of a structure focus or it can act as a screening step for a subsequent, more computationally intensive technique to accomplish, for example, electrostatic similarity. 

The atom pair, ap, and topological torsion, tt, descriptors are selected for illustrative purposes in the similarity searching context. 

ExPASy Proteomics tools (http //expasy.org/tools/), tools and online programs for protein identification and characterization, similarity searches, pattern and profile searches, posttranslational modification prediction, topology prediction, primary structure analysis, or secondary and tertiary structure prediction. 

The second step comprises similarity searches from known ligands using 2-D descriptors like fingerprints, topological descriptors like atom-pair fingerprints. 

Diederichs, K. Structural superposition of proteins with unknown alignment and detection of topological similarity using a six-dimensional search algorithm. Proteins Struc., Func., Genet. 1995, 23, 187-195. 

The concept of chemistry space pervades, either explicitly or implicitly, much of the literature in chemoinformatics. As is discussed in Subheading 3., chemistry spaces are induced by various similarity measures. The different similarity measures do not, however, give rise to topologically equivalent chemistry spaces—nearest-neighbor relations are generally not preserved among chemistry spaces induced by different similarity measures. The consequences of this are manifold. An especially egregious consequence is that the results of similarity searches based on different similarity measures can differ substantially. And there is no easy solution to this problem. 

An example may help to clarify this statement Figure 13.4 shows the 10 highest-ranking compounds that were retrieved from the COBRA database by a topological pharmacophore similarity search (CATS method, see below). The query structure was Haloperidol, a dopamine (D2) receptor antagonist. Not surprisingly classic variations of the query structure are found in ranks 1 and 2. These are not very... 

Figure 13.4 Results of a CATS similarity search. Similarity between the query structure (Haloperidol, a D2 antagonist upper left) and database compounds was defined in terms of a topological pharmacophore descriptor. The top 10 most-similar molecules found are shown.

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