Structure and Function of Molecular
Systems
Obrázek 1. Struktura
a-dihydrátu kyseliny oxalové [2]. Atomy se nacházejí s 50% uvnitř termálních
elipsoidů. Označeny jsou jen atomy ze symetricky nezávislé části, uprostřed C-C
vazby je krystalografický střed symetrie.
Cambridge Crystallographic Data Centre (CCDC) provides scientific community by database containing more than 250 thousands organic and organometalic compounds with 3D structure determined by X-ray crystallography – Cambridge Crystallographic Database (CSD). In addition to CONQUEST – the basic program for searching the CCDC database [1] – the CCDC distributes programs for analysis of intra and inter-molecular interactions - QUEST, PREQUEST, MERCURY, VISTA, ISOSTAR, SUPERSTAR, GOLD and DASH. In addition to that, there is other software working directly with output data from CCDC runs [3].
The CCDC software gives us excellent tool for searching various features in experimentally determined structures by X-rays or NMR. It provides routines for statistical analysis of structure changes and for analysis of relations between the structure and function. Especially, it allows direct evaluation of effects connected with weak intermolecular interactions. Software works with any type of molecules no regard if they are from CCDC [1] or PDB [2] databases. The following text gives a short characterization of the software mentioned above.
CONQUEST – Windows and UNIX based versions of the user friendly and screen oriented database searching tool. User has wide range of possibilities for searching of molecular fragments including many detailed geometrical restrictions.
QUEST – Original Unix version of the CSD database searching tool.
PREQUEST – Software allowing the user to add his own structures to the local installation of database and include his own data in his statistics and charts. The program reads in the CIF or SHELX formated files and produces keywords (1D), chemical diagrams (2D), crystallographic connectivity (3D), etc.
MERCURY – Software for easy viewing and 3D analysis of interactions in crystalline material. It is extremely useful namely for large molecules and molecules forming complex space networks and for searching for main features forming the crystal structure.
VISTA – Tool for statistical analysis of data extracted from CSD. Specialized tools for spreadsheets, modification of input data, plotting histograms and scattergrams.
ISOSTAR ver.1.5 – A collection of statistical analyses of intermolecular interactions containing 25022 scatterplots and 1550 theoretical studies derived from X-ray and NMR determined structures of 257162 organic and organometalic compounds and 7021 protein-ligand complexes. It describes combinations of 350 central function groups and 45 contact groups. User can view three dimensional distribution of frequency occurrence of intermolecular contacts (so called density surfaces). User has a possibility to add his own structures and prepare his own statistical analysis locally.
RELIBASE – Software and database of intermolecular interactions based on the macromolecular PDB database [2]. It is build on about 20 000 macromolecular structures determined by X-ray and NMR techniques. It gives total 97134 individual ligand binding sites with ligands (substrates, inhibitors) either experimentally found or docked into the experimentally verified protein structure.
SUPERSTAR – a program identifying interaction sites in proteins. The propensity 3D maps highlight hot spots for interaction with ligands (e.g. protein binding sites).
GOLD (Genetic Optimization for flexible Ligand Docking) - program for docking of flexible ligands into protein binding sites. It uses formally SYBYL atom and bond types, however the force field and constraints used are quite different and are strongly based on the experimental data found on similar structures in the structure databases [1],[2]. Program requires correct connectivity of hydrogen atoms, however no care is necessary for their orientation, for conformation of ligand and protein side chains because the program uses an efficient genetic algorithm for global search for optimal conformations of ligands and all flexible side chains of protein. It docks well metal ions Mg, Zn, Fe, Mn, Ca, Co, Gd.
DASH – Software for crystal structure determination from powder diffraction data. Program uses simulated annealing to adjust the original trial structure model so that it fits better the measured diffraction record.
The CCDC database is re-newed biannually and is distributed on the bases of national licenses [3]. The access to data and the license for basic software QUEST, PREQUEST, MERCURY, VISTA and ISOSTAR is paid each year by the Crystallographic Association in frame of the project of the Grant Agency of the Czech Republic (contractor Jan Ondráček). The network access is available free of charge for any non-commercial user from the Czech Republic via computer centre of the Physical Institute of the Czech Academy of Sciences – e-mail address fabry@fzu.cz.
Another possibility to use CSD is to install your local version of CONQUEST under MS Windows on your PC. The year license for one additional PC version of CONQUEST (70 GBP) gives you the easiest way to work with CSD. The software GOLD (1250 USD), DASH (500 USD) and SUPERSTAR (license 90 GBP each year) is distributed as local licenses only. Information on all the license conditions concerning the CCDC is available at hasek@imc.cas.cz and the website references [1], [3].
Local support for new users of CSD is available at the following places:
Computer centre enabling a
network access:
Jan Fábry, FZÚ AV ČR, Na Slovance, Praha 8 fabry@fzu.cz
Local instalation sites:
Jan Ondráček, ÚMG AV ČR, Flemingovo nám. 2, Praha 6 ondracek@zeus.img.cas.cz
Jaromír Marek, Masarykova universita, Brno marek@chemi.muni.cz
Jindřich Hašek, ÚMCH AV ČR, Heyrovského nám. 2, Praha 6 hasek@imc.cas.cz
Ivana Kutá-Smatanová, JČU, Nové Hrady ivas@bf.jcu.cz
[1] CCDC documentation website:
http://www.ccdc.cam.ac.uk/support/csd_doc/
[2] PDB website: http://www.rcsb.org/pdb/
[3] National Affiliated Centre of CCDC: http://www.xray.cz/ccdc/