Query structure, specification

A number of other software packages are available to predict NMR spectra. The use of large NMR spectral databases is the most popular approach it utilizes assigned chemical structures. In an advanced approach, parameters such as solvent information can be used to refine the accuracy of the prediction. A typical application works with tables of experimental chemical shifts from experimental NMR spectra. Each shift value is assigned to a specific structural fragment. The query structure is dissected into fragments that are compared with the fragments in the database. For each coincidence, the experimental chemical shift from the database is used to compose the final set of chemical shifts for the... 

If one s purpose is to determine only the presence or absence in a data base of a specific structure, this can be accomplished with the search option IDENT , as is shown in Figure 11. This program hash-encodes the query structure connection table and searches through a file of hash-encoded connection table for an exact match. The search, which is very fast by substructure search standards, has been designed specifically for those users who, to comply with the Toxic Substances Control Act [26l have to determine the presence or absence of specific compounds in Environmental Protection Agency files. 

Finally, if one has completed ring probe and fragment probe searches for a specific query structure and is still confronted with a sizeable file of compounds that satisfy the criteria that were nominated, a sub-structure search through this file may be carried out. This involves an atom-by-atom, bond-by-bond comparison of every struc-... 

Fig. 4.10 Generating a query structure for virtual screening of j8-secretase inhibitors. The combined query structure used for screening is the result of the combination of a common pharmacophore derived from 95 known peptide inhibitor—aspartyl-protease complexes and a target-specific pharma-...

It may be the case that the searcher is interested in structures (a), (b) and (c), whereas he is not at all interested in (d) and (e) because they are structurally too general. The differences in structural generalisation are clearly revealed within the partial structure representations of the ECTR. The alternative partial structures of (a) are represented as partial connection tables whereas (b) to (e) are represented by parameter lists where the different levels of generalisation are indicated by differences in the integer ranges of particular parameters as shown in Table 3. Table 3 also contains the specific-derived parameter lists of the corresponding query structure (g) and the two alternative specifics within (a), t-butyl (al) and i-propyl (a2). 

The screen generation process identifies specific structural features present in the structures. These features are called screens or screen fragments and are described in more detail below. The screens generated for query structures are formulated into a screen search logic expression and sent to the screen search phase. Screens generated for file structures are sent to the appropriate file loading systems. 

The underlying composite generic and specific structure (see Section 3.3.2.1(b) above) allows for fuzzy structure search. The ability to tag portions of a query structure is limited to a generic group basis. On the basis of such portions in fuzzy structure search, one can range from the exactness of substructure search to the fuzziness of a similarity search (the default). 

The three basic methods and their extensions described so far are mainly used for spectrum prediction in this case the correlation of a particular carbon atom within a certain environment with its specific chemical shift value is necessary and must be accessed during spectrum prediction. During the spectrum prediction process the query structure is analyzed in terms of single carbon atoms with their environments this information is checked against a lookup table and for each carbon a certain shift value is predicted. The final result is obtained by repeating this process for each carbon atom independently. 

Substructure searching is the process of identifying the members of a set of chemical moieties that match a specific query moiety. In most applications, the problem corresponds to mapping a query structure, usually containing free valency sites and variable atom or bond attributes, on to a set of target structures stored in a database. 

The usefulness to the WRAIR Staff of searching for substructures on-line has yet to be determined. Since the chemistry retrieval system uses the screen and connection teible generated by the query to search to screen index file for either a whole or a sub-structure no more information (disk-drives) is needed on-line for sub-structure searching than for identity matches, so one is no more costly than the other, in terms of disk resources. But the elapsed time needed for such sub-structure searches varies greatly and may be large. The time needed may be kept small if the query is specific and many screen bits are set. 

Offline preparation and presentation of chemical structure graphics is now possible on a PC using a variety of query editor programs (7), such as those listed in Figure 3. In most cases these are specific to a single system, and use a proprietary format for transmission of the query structure between the PC and the mainframe computer. For example, STN Express allows query structures to be built offline and then, after connection to STN, uploaded and searched against the STN online structure files. Retrieved structures can be downloaded onto the PC and browsed offline in STN Express. Similarly, CHEMLINK is now available for Telesystemes-DARC, while in the case of in-house systems, ChemBase provides similar capabilities for MACCS. 

Substructure searches provide another method of searching for available starting materials. They arc used primarily for planning the synthesis of combinatorial libraries. After the target compound has been dissected into a set of suitable precursors, substructure searches can provide for each of them a series of representatives of a certain class of compounds, Siibsti ucturc searches enable the user to specify attributes such as open sites or atom lists at certain positions of the structure. Figure 10.3-38 shows the possible specification elements for the query in a substructure search. 

CHIRBASE provides integrated responses from single questions, as well as from combinatorial questions constructed on the basis of any specific query corresponding to one or several field(s) occurring in the database. With the molecular structure of a sample in hand, the search can be conducted interactively from the query menu form. 

Structure and substructure searching are very powerful ways of accessing a database, but they do assume that the searcher knows precisely the information that is needed, that is, a specific molecule or a specific class of molecules, respectively. The third approach to database searching, similarity searching, is less precise in nature because it searches the database for molecules that are similar to the user s query, without formally defining exactly how the molecules should be related (Fig. 8.3). 

The CrossFire Beilstein database is the world s largest compilation of chemical facts. This database indexes three primary data domains substances, reactions and literature. The substance domain stores structural information with aU associated facts and literature references, including chemical, physical and bioactivity data. The reaction domain details the preparation of substances, enabling scientists to investigate specific reaction pathways with reaction search queries. The literature domain includes citations, titles and abstracts, which are hyperhnked to the substance and reaction domain entries. It contains over 320 million experimental data, over 10 million reactions and data indexed from over 175 journals. 

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