Three-dimensional structure/substructure searching

Biological macromolecules present special problems for substructure searching. In many cases the feature of interest is the one-dimensional sequence of amino-acid or nucleotide residues, and a number of databases of such sequences are now available for searching. Searching of the three-dimensional structure of such macromolecules is also of interest. ... 

A module of the CHEM-X modelling system (see modelling section). Storage and retrieval of two- and three-dimensional structures with substructure-search capability. Available databases include Chapman Hall Dictionary of Drugs (15,000 compounds). Chapman Hall Dictionary of Fine Chemicals (120,000 small organics). Chapman Hall Dictionary of Natural Products (54,000), Derwent Standard Drug File (31,000 biologically active compounds), ChemReact (370,000 reaction types) and others. 

Recently, Wipke and Rogers described superstructure searching, which retrieves those molecules that are contained within the query structure, rather than the inverse. The same bit maps are used the difference is that for a substructure search the bit screen of the hit must contain all of the query bits, whereas for a superstructure search the query must contain all of the bits present in the hit. This type of search has applications in computer-aided design of synthetic pathways and in building three-dimensional structures from three-dimensional fragments. ... 

An important distinaion between ALADDIN and the other programs described in this section is that the user specifies at the time of the search the substructural environment of the atoms and the definition of the geometric objects. This is one key to its flexibility. Another distinction is its close tie to molecular graphics with not only the three-dimensional structure, but also the hit atoms identified for the graphics program. A final distinction is that it has provisions for automatically generating both the two-dimensional and three-dimensional structures of molecules proposed for synthesis. 

Third, there is a need to be able to integrate the basic searching facilities with the more sophisticated routines for three-dimensional structure matching that have been described in this review. ° ° ° An obvious related area is the use of three-dimensional structures to derive descriptors for quantitative structure-aaivity relationships. This could be either an extension of the wide use of two-dimensional fragments for substructural analysis stud-ies 8 8i to three-dimensional fragments, or the automatic generation of data for a prediction of potency, e.g., the recent work of Cramer et al. ° ... 

Inorganic Three-dimensional Structure Databases Molecular Docking and Structure-based Design Protein Data Bank (PDB) A Database of 3D Structural Information of Biological Macromolecules Structural Similarity Measures for Database Searching Structure and Substructure Searching Structure Databases Structure Representation Three-dimensional Structure Searching,... 

Structural Similarity Measures for Database Searching Structure and Substructure Searching Three-dimensional Structure Searching Topological Indices... 

Van drie, J.H., Weininger, D., and Martin, Y.C. ALADDIN an integrated tool for computer-assisted molecular design and pharmacophore recognition from geometric, steric, and substructure searching of three-dimensional molecular structures./. Comput.-Aided Mol. Des. 1998, 3, 225-251. 

The previous section shows how molecular structures stored in an RDBMS can be made available to client programs that traditionally read molecular structure files. The advantage of storing molecular structures in an RDBMS is that the information can be used from within the database, as well as by external clients. For example, it would be possible to search a table of molecular structures for three-dimensional overlap, much like it might be searched for substructure match. Of course, such search functions need to be written and installed as extensions to an RDBMS, just like the matches functions was done for substructure searches. This section shows some possible ways this might be accomplished. 

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