Database continued illustrations

The hierarchy of protein structure is illustrated in hgure 11.4. Here too we have a wealth of structural information. The quaternary structures for many proteins are now known and generally available in databases. As complex as these are, this is not the end of the story. We have atom-by-atom structures for entities as complex as viruses and the ribosome, an intracellular RNA-protein complex and the site of protein synthesis. Modem structural biology continues to provide detailed insights into some of the most complex constracts of nature. We are better off for having these insights. 

The concepts of molecular similarity (1-3) and molecular diversity (4,5) play important roles in modern approaches to computer-aided molecular design. Molecular similarity provides the simplest, and most widely used, method for virtual screening and underlies the use of clustering methods on chemical databases. Molecular diversity analysis provides a range of tools for exploring the extent to which a set of molecules spans structural space, and underlies many approaches to compound selection and to the design of combinatorial libraries. Many different similarity and diversity methods have been described in the literature, and new methods continue to appear. This raises the question of how one can compare different methods, so as to identify the most appropriate method(s) for some particular application this chapter provides an overview of the ways in which this can be carried out, illustrating such comparisons by,... 

The availability of a great number of data obtained with different radioligands, membrane preparations, different tissue sources and differences in the assay conditions makes the comparison of receptor profile of clozapine, olanzapine and quetiapine (as well as other antipsychotics) extremely difficult This issue has become even more complicated since the availability of recombinant receptors from various species expressed in various expression systems that resulted in a continuously growing number of K, data and further additions to the receptor profile. (For example, in May 2005, when the latest search in the database http // kidb.cwru.edu/pdsp.php was made, 464, 272, and 156 K, values for various receptors and transporters were recorded for clozapine, olanzapine, and quetiapine, respectively, representing an average K, growth rate of 11 to 16 per month over the past five months.) Different data from the same authors obtained at different times further complicate the comparisons. The receptor K, data in Tab. 13.1 illustrate the situation to some extent. 

Vacuum forming has and is likely to continue to lose a share of both the European and North American fleets. The trend line based on REA s European instrument-panel database multiclient study (10) is illustrated in Eigure 3 for the European market. Vacuum-formed TPO skins (both compact [skin only] and composite [skin/foam laminates]) have gained some share at the expense of PVC/ABS skins, but this has not arrested the decline of vacuum-formed IP skins in favor of slush molding. Negative forming (e.g., Honda Civic IP skin) has... 

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