Family Structure Search

The sequence of a protein of interest can be compared with all other known sequences to ascertain whether significant similarities exist. Does this protein belong to an established family A search for kinship between a newly sequenced protein and the millions of previously sequenced ones takes only a few seconds on a personal computer (Chapter 6). If the newly isolated protein is a member of an established class of protein, we can begin to infer information about the protein s structure and function. For instance, chy-motrypsin and trypsin are members of the serine protease family, a clan of proteolytic enzymes that have a common catalytic mechanism based on a reactive serine residue (p. 245). If the sequence of the newly isolated protein shows sequence similarity with trypsin or chymotrypsin, the result suggests that it may be a serine protease. 

A structure search of chemical substances can be performed in the chemical structure databases. The structure query can be input using a graphical structure editor. The following search methods are possible, depending on the type of structure database. The structure search capabilities depend on the software system. Here, the focus is on the implementation of STN International exact structure search, family search, substructure search, similarity search, generic (Markush) search, and reaction search. 

Like the Exact Structure Search, Family Searches (FAM) also do not allow further substitutions. The result consists of compounds that match exactly the request, and also of multicomponent substances as well as salts, such as the potassium salt of piceol in Fig. 100. 

Unlike the Registry File, which contains single, exactly defined compounds, MARPAT provides numerous compounds under a single structure. Since only generic structures are contained in MARPAT, Exact (EXA) and Family Searches (FAM) cannot be executed - it is only possible to conduct Closed Structure Searches (CSS) and Substructure Searches (SSS) (Sect. 7.2.1). 

Taxonomically close to the Annonaceae, the Lauraceae family abounds with apor-phinoid alkaloids. A remarkable advance in the search for topoisomerase inhibitors from Lauraceae has been provided by Woo et al. (6). Using DNA-unwinding assay and structural modeling, they showed that dicentrine can attain a relatively planar conformation and molecular bulk which allow it to occupy the active site of topoisomerase II which becomes inactive. The requirement of a suboptimal conformation to achieve DNA binding appears to make dicentrine less potent against topoisomerase II than the... 

While the number of references in the literature pertaining to applications of the 1,1-ADEQUATE experiment is sparse, there is almost a complete dearth of papers citing applications of the 1,/ -ADEQUATE experiment. Aside from the development of the ADEQUATE family of experiments in which the 1,/ -ADEQUATE experiment was described, and some correlations for 5,6-dihydrolamellarin (3) that were reported in the elucidation of that structure (see Section 4.1), there are only a few papers that appear in literature searches. 

On the other hand, there is considerable interest to quantify the similarities between different molecules, in particular, in pharmacology [7], For instance, the search for a new drug may include a comparative analysis of an active molecule with a large molecular library by using combinatorial chemistry. A computational comparison based on the similarity of empirical data (structural parameters, molecular surfaces, thermodynamical data, etc.) is often used as a prescreening. Because the DFT reactivity descriptors measure intrinsic properties of a molecular moiety, they are in fact chemical fingerprints of molecules. These descriptors establish a useful scale of similarity between the members of a large molecular family (see in particular Chapter 15) [18-21],... 

It can be difficult if not impossible to find the domain structure of a protein of interest from the primary literature. The sequence may contain many common domains, but these are usually not apparent from searches of literature. Articles defining new domains may include the protein, but only in an alignment figure, which are not searchable. Perhaps, with the advent of online access to articles, the full text including figures may become searchable. Fortunately there have been several attempts to make this hidden information available in away that can be easily searched. These resources, called domain family databases, are exemplified by Prosite, Pfam, Prints, and SMART. These databases gather information from the literature about common domains and make it searchable in a variety of ways. They usually allow a researcher to look at the domain organization of proteins in the sequence database that have been precalculated and also provide a way to search new sequences... 

A domain family that is considerably expanded in nematodes, relative to vertebrates, is the zona pellucida (ZP) domain (Bork and Sander, 1992). In database searches this domain was found in C. elegans cuticlin-1 (cut-1), a component of the nematode cuticle (Sebastiano et al., 1991), and 33 other C. elegans proteins (Table II). On the basis of disulfide-linked domains that accompany the ZP domain in these proteins, it is likely that they localize to the worm s extracellular matrix. Indeed, it is possible that most of these proteins are components of the worm cuticle. The cuticle structure is the multilayered elastic exoskeleton that determines the worm s body shape. Although vertebrates lack an equivalent... 

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