Crystallographic database

Abstract: Finding novel leads from which to design drug molecules has traditionally been a matter of screening and serendipity. We present a method for finding a wide assortment of chemical structures that are complementary to the shape of a macromoleculer receptor site whose X-ray crystallographic structure is known. Each of a set of small molecules from the Cambridge Crystallographic Database (Allen; et al. J. Chem. Doc. 1973, 13, 119) is individually docked to the receptor in a number of geometrically permissible orientations with use of the docking algorithm developed by Kuntz et al. (J. Mol. Biol. 1982, 161, 269). The orientations are evaluated for goodness-of-fit, and the best are kept for further examination using the molecular mechanics program AMBER (Weiner; Kollman J. Comput. Chem. 1981, 106, 765). The shape-search algorithm finds known ligands as well as novel molecules that fit the binding site being studied. The highest scoring orientations of known ligands resemble binding modes generated by interactive modeling or determined crystallographically. We describe the application of this procedure to the binding sites of papain and carbonic anhydrase. While the compounds recovered from the Cambridge Crystallographic Database are not, themselves, likely to be inhibitors or substrates of these enzymes, we expect that the structures from such searches will be useful in the design of active compounds.

Abstract: MINCRYST is an original interrelated combination of the Crystal Structure Database for Minerals, Subbase of Calculated Polycrystal Standards (Calculated Powder X-ray Diffraction Standard Subbase, CPDS Subbase), and the Applied Program Package. The Information fund of the Crystal Structure Database comprises about 4800 files. Two MINCRYST versions are developed—the local (L) version with the original Database Management System designed for use on a personal computer and the WWW version with an original interface integrated into the WWW server of the Institute of Experimental Mineralogy of the Russian Academy of Sciences (Chernogolovka) accessible to all the Internet users.

Abstract: A search method for investigating the extent to which chloro-methyl interchange is exhibited by crystal structures deposited with the Cambridge Crystallographic Database is presented. Using the October 1998 release with 190,307 data entries, 105 pairs were identified for which there was a common molecular framework, differing only in the presence of a chloro or methyl group. Approximately 30% appear to demonstrate isotructural packing arrangements. Two examples within the database that were found not to show Cl-Me interchange were subsequently examined from the viewpoint of structural mimicry and the formation of mixed crystals.