Similarity searching some examples

Current chemical information systems offer three principal types of search facility. Structure search involves the search of a file of compounds for the presence or absence of a specified query compound, for example, to retrieve physicochemical data associated with a particular substance. Substructure search involves the search of a file of compounds for all molecules containing some specified query substructure of interest. Finally, similarity search involves the search of a file of compounds for those molecules that are most similar to an input query molecule, using some quantitative definition of structural similarity. 

Asymmetric similarity can provide some benefits in similarity searches not afforded by its symmetric competitors. For example, consider as in Subheading 2.2.1., the query and target molecules, Q and T, respectively, and the asymmetric similarity coefficients given in Eqs. 2.26 and 2.27. If Q is relatively small (N.B. small and large are used here refer to the size of the set and not to the size of the corresponding molecule), that is, if Q T, then target molecules for which Q is an approximate subset will be selected using Eq. 2.26, that is,... 

Similarity Searching with Pharmacophore Fingerprints - Some Examples... 

A similarity search provides a way forward by retrieving the structures that are similar, but not identical, to a lead compound (94). Therefore, it overcomes some limitations of substructure search, for example, not requiring specific knowledge about the substructures responsible for activity, and being able to rank the output structures accordingto the overall similarity. The search query usually involves a set of descriptors that collectively specify the whole structure of the lead compound. This set of descriptors is compared with the corresponding set of descriptors for... 

There are many other substances, however, which do not have these properties. These non-ionic substances are so numerous that it is not necessary to search for examples—nearly every substance except the salts is in this class. Thus molten sulfur, like solid sulfur, is an electrical insulator. Liquid air (liquid oxygen, liquid nitrogen), bromine, gasoline, crrbon tetrachloride, and many other liquid substances are insulators. Gases, too, are insulators, and do not contain ions, unless they have been ionized by an electrical discharge or in some < similar way. 

Factor analysis is a method by which correlations among all variables are searched for simultaneously. The overall aim (in a crystallographic context) is to analyze molecular geometry from a set of similar structures, some of which are of limited precision, and find out if there are any significant effects that stand out from the noise due to experimental errors. In the example of five-coordinate complexes of d metals by Biirgi and Auf der Heyde (described above), a factor analysis indicated that the difference between the elevated and flattened pyramids is significant. 

The results for a Py-GC/MS analysis of a sample of poly(vinyl toluene) (mixed isomers) CAS 9017-21-4, Mw = 80,000 are shown in Figure 6.2.17. The pyrolysis was done from 0.4 mg material at 600° C in He at a heating rate of 20° C/ms with 10 s THT. The separation was done on a Carbowax column similar to other examples previously discussed (see Table 4.2.2). The peak identification for the chromatogram shown in Figure 6.2.17 was done using MS spectrai library searches only and is given in Table 6.2.11. Some of the isomer positions are tentative only and reported in Table 6.2.11 as they resulted with the highest probabiiity indicated by the mass spectral library search. 

Preliminary hit follow-up was accomplished by performing similarity searches on databases of commercially available analogues (Fig. 2). In this initial phase, 50 commercial analogues were identified, purchased, and tested for their ability to inhibit TNAP. This allowed us to define some important features of the SAR. For example, the potency in this series was improved from IC5o = 0.98 pM for the lead pyrazole 1 to IC5o = 0.50 pM for the... 

On this basis, the structure we have used for our example can be analyzed in the manner described to produce a series of three short codes, which describe not only this molecule, but also any nongeminal combination of the two substituents around the ring (see Figure 5). This is a really a similarity search in chemical structures, a capability which is complementary to a substructure search, and has some relevance for certain types of Markush representation- A brief inspection of the "chemical environment" of any randomly chosen region of ca. 30 pages of the Handbook will demonstrate the strengths and limitations of this approach. 

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