Section 22.4.3. Structural knowledge from the CSD

Structural knowledge from the CSD is reflected principally in the geometries of individual molecules, extended crystal structures and, most importantly, through systematic studies of the geometrical characteristics of large subsets of related substructural units. Software facilities for search, retrieval, analysis and visualization of CSD information are fully described in Chapter 24.3 . The system allows for the calculation of a very wide range of geometrical parameters, both intramolecular and intermolecular. Most importantly, chemical substructural search fragments may be specified using normal covalent bonding definitions (single, double, triple etc.), limiting non-covalent contact distances and other geometrical constraints. For each instance of a search fragment located in the CSD, the system will compute a user-defined set of geometrical descriptors. The full matrix, G(N, p), of the p geometrical parameters for each of the N fragments located in the CSD can then be analysed using numerical, statistical and visualization techniques to display individual parameter distributions, to compute medians, means and standard deviations, and to examine the geometrical data for correlations or discrete clusters of observations that may exist in the p-dimensional parameter space.

Table 22.4.3.1 presents statistics for the 3137 structures of amino acids and peptides that are available in the CSD of April 1998 (containing 181 309 entries). Although this represents less than 2% of CSD information, some may consider that these are the only entries of real interest in molecular biology. In certain cases, e.g. for the derivation of very precise molecular dimensions and for some conformational work, this may be true. However, the real issue concerns the transferability of CSD-derived information to the protein environment. It is the biological relevance of a chemical substructure (inter- or intramolecular) that is important, and this consideration immediately brings much larger subsets of CSD entries into play. Information such as van der Waals radii can be derived from the CSD as a whole, while more specific information concerning, for example, biologically important metal coordination geometries can be derived from appreciable subsets of the total database, as shown in the statistics of Table 22.4.3.2.

Precise geometrical knowledge from atomic resolution studies of small molecules is important in the macromolecular domain since it provides: (a) geometrical restraints and standards to be applied during protein structure determination, refinement and validation; (b) model geometries for liganded small molecules and information about their preferred modes of interaction with the host protein; (c) details of metal coordination spheres and geometries that are likely to be observed in metalloproteins; and (d) information from which force field and other parameters may be derived. Thus, the types of study discussed in this chapter are concerned with retrieving systematic knowledge concerning:

In this short overview, which deals with such a broad range of structural information, our literature coverage is, of necessity, highly selective. In each area, we have tried to cite the more recent papers, from which leading references to earlier studies can be located. We also draw attention to a number of recent monographs in which a variety of CSD analyses are comprehensively cited and discussed: Structure Correlation (Bürgi & Dunitz, 1994), Crystal Structure Analysis for Chemists and Biologists (Glusker et al., 1994), Hydrogen Bonding in Biological Structures (Jeffrey & Saenger, 1991) and Crystal Engineering: the Design of Organic Solids (Desiraju, 1989). Finally, we note the CCDC's own database of published research applications of the CSD. The DBUSE database currently contains literature references and short descriptive abstracts for nearly 700 papers. It forms part of each biannual CSD release and is fully searchable using the Quest3D program.