Databases, structural

Although not being in the focus of this chapter, structural databases are a most useful resource for the scientist interested in enzymes and reaction mechanisms. The Protein Data Bank (PDB) is the main repository for all three-dimensional structures of macromolecules including enzymes 55. Nowadays, most journals accepting manuscripts that describe new structures require a simultaneous deposition of the structural coordinates with the PDB database. In addition to the structure of single protein molecules, the PDB also contains several entries of multi-protein complexes, or proteins bound to small-molecule compounds. 

Of the 14500 entries currently in PDB, there are roughly 7200 enzyme structures. The Enzymes Structures Database, maintained by University College, University of London, focuses on this portion of PDB and offers links between the E.C. nomenclature of the IUBMB and the corresponding PDB entries. 

It should be remembered that a crystallographic database can only provide information about the crystalline state of matter, and that the possible influence of crystal packing forces should always be taken into account. This is less of a concern for proteins than for small molecules as protein crystals contain a large amount of water and indeed NMR studies have established that proteins have approximately the same structure in solution as in the crystal. A second, more subtle, bias is that crystallographic databases contain only molecules that can be crystallised and indeed only those molecules whose X-ray structures were considered important enough to be pubhshed. The structures in a crystallographic database may therefore not necessarily be a wholly representative set. 

The co-ordinates of a structure on their own are of very limited value. To use them and to be able to capitalise on the potential value of the database, it is necessary to employ computer graphics programmes which enable the structures of proteins to be represented graphically, preferably in three dimensions. 

Abrahams, J.P., Kraal, B. Bosch, L. (1988) Zone Interference Gel Electrophoresis A New Method for Studying Weak Protein-Nucleic Add Complexes under Native Conditions, Nucleic Acids Res. 16,10099-10108. 

Pecora, R. (1976) Dynamic Light Scattering with Applications to Biology, Chemistry, and Physics. John Wiley Sons, New York. 

Johnson, M.L (1997) Fluorescence Spectroscopy. Methods. Enzymol. Volume 278. 

Burlinghame, A.L., Carr, S.A. (Eds.) (1999) Mass Spectrometry in Biology and Medicine. Humana Press, Totowa, NJ. 

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As source of infonnation we use the Surface Structure Database [14], a critical compilation of surface structures solved in detail, covering the period to the end of 1997. It contains 1113 structural detenninations with, on average, two detenninations for each stmcture thus there are approximately 550 distinct solved stnictures available. 

Watson P R, Van Hove M A and Hermann K 1999 NIST Surface Structure Database Ver. 3.0 (Gaithersburg, MD NIST Standard Reference Data Program)... 

The JME Editor is a Java program which allows one to draw, edit, and display molecules and reactions directly within a web page and may also be used as an application in a stand-alone mode. The editor was originally developed for use in an in-house web-based chemoinformatics system but because of many requests it was released to the public. The JME currently is probably the most popular molecule entry system written in Java. Internet sites that use the JME applet include several structure databases, property prediction services, various chemoinformatics tools (such as for generation of 3D structures or molecular orbital visualization), and interactive sites focused on chemistry education [209]. 

The JME can also serve as a query input tool for structure databases by allowing creation of complex substructure queries (Figure 2-130), which are automatically translated into SMARTS [22]. With the help of simple HTML-format elements the creation of 3D structure queries is also possible, as were used in the 3D pharmacophore searches in the NCI database system [129]. Creation of reac-... 

Typical numeric databases are Beilstein, Speclnfo, DETHERM, and the Cambridge Structural Database. 

Structure databases are databases that contain information on chemical structures and compounds. The compounds or structure diagrams are not stored as graphics but are represented as connection tables (see Section 2.4). The information about the structure includes the topological arrangement of atoms and the connection between these atoms. This strategy of storage is different from text files and allows one to search chemical structures in several ways. 

Examples of structure databases are Beilstein, Gmehn, and CAS Registry. 

The two major databases containing information obtained from X-ray structure analysis of small molecules are the Cambridge Structural Database (CSD) [25] and the Inorganic Crystal Structure Database (ICSD) [26] both are available as in-house versions. CSD provides access to organic and organometallic structures (mainly X-ray structures, with some structures from neutron diffraction), data which are mostly unpublished. The ICSD contains inorganic structures. 

The Cambridge Structural Database (CSD) contains crystal structure information... 

Compounds are stored in reaction databases as connection tables (CT) in the same manner as in structure databases (see Section 5.11). Additionally, each compound is assigned information on the reaction center and the role of each compound in the specific reaction scheme (educt, product, etc.) (see Chapter 3). In addition to reaction data, the reaction database also includes bibliographic and factual information (solvent, yield, etc.). All these different data types render the integrated databases quite complex. The retrieval software must be able to recall all these different types of information. 

They are classified as bibliographic, factual, and structure databases. 

The Cambridge Structural Database (C5D) and the Inorganic Crystal Structure Database (ICSD) contain information obtained from X-ray structure analysis. 

The first task was the aeation of large 3D chemical structure databases. By devising so-called fast Automatic 3D model builder, software such as the CORINA [27, 28] and CONCORD [29, 30] programs resulted in a boom in 3D database development (see Section 2.9 in this book and Chapter II, Section 7.1 in the Handbook). A subsequent step was the development of fast... 

The abbreviation QSAR stands for quantitative structure-activity relationships. QSPR means quantitative structure-property relationships. As the properties of an organic compound usually cannot be predicted directly from its molecular structure, an indirect approach Is used to overcome this problem. In the first step numerical descriptors encoding information about the molecular structure are calculated for a set of compounds. Secondly, statistical methods and artificial neural network models are used to predict the property or activity of interest, based on these descriptors or a suitable subset. A typical QSAR/QSPR study comprises the following steps structure entry or start from an existing structure database), descriptor calculation, descriptor selection, model building, model validation. 

The structure database has been enriched with the 3D structures of all compounds as generated by the 3D structure generator CORINA (sec Section 2.9,... 

We can contrast these methods using the data shown in Figure 9.30, which were obtained by searching the Cambridge Structural Database for the ribose phosphate fragment also shown... 

Fig. 9.30 Ribose phosphate fragment used to extract data from Cambridge Structural Database and eight sets 0 torsion angle values for tj and r. ...

Downs G M, P Willett and W Fisanick 1994. Similarity Searching and Qustering of Chemical Structure Databases using Molecular Property Data, journal of Chemical Information and Computer Sciences 34 1094-1102. 

A number of structured databases have been developed to classify proteins according to the three-dimensional structures. Many of these are accessible via the World Wide Web, T1 protein databanlc (PDB [Bernstein d al. 1977]) is the primary source of data about the stru tures of biological macromolecules and contains a large number of structures, but many i these are of identical proteins (complexed with different ligands or determined at differet resolutions) or are of close homologues. 

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