Cambridge Structural Database

Crystal Structures of Small Organic and Organometallic Compounds

Dr. Clifford Felder (Clifford.Felder@weizmann.ac.il, phone 3077) Dept. of Structural Biology, Weizmann Institute, ? ???. 2005/6

I am presenting here the new program ConQuest, which runs both in Unix/Linux andMS Windows. It requires purchasing a license for every computer it is installed on.

However, the Unix version can be run remotely over the network under windows-X11.

Unfortunately, the older, free program questv5, is no longer supported.

The CSDS provides some auxilliary programs for more specialized functions, seetheir Web site for details. We will present here two programs, Mercury and Vista.

The Cambridge Database Home Page is at http://www.ccdc.cam.ac.uk/

Two Kinds of Searches:1) Geometric Properties: structures of specific functional groups, bond lengths and angles, non-bonded interactions, statistical and correlation studies.2) Specific Compounds: ligands and drugs to dock into protein receptors, initial coordinates for X-ray refinement programs, literature checks.

Searches for Specific Compounds and Structures: Initial Cartesian Coordinates of Ligands or Drugs: - to dock into protein receptor active sites - for X-ray structure refinement or molecular mechanics (Note: the X-ray conformation may not be correct in this context!) Obtain Cartesian Coordinates for X-ray structures Published in the Literature - Literature checks of published structures

Geometric Property Analyses: Accurately Characterize a Functional Group or Groups: - Tabulate All or Selected Bond Lengths and Angles - Degree of Planarity - Rotation about Bonds: cis vs. trans, 3-fold, freely rotating Nonbonded Interactions: - Close contact distances - Charge-charge and hydrophobic interactions - Hydrogen bonding - Cation-pi, pi-pi and other kinds of interactions - Define centroids, vectors and planes Analize Distributions of, and Correlations between Properties.

To Run ConQuest Remotely via the Campus Network

1) Locate a Unix computer on the campus network that has ConQuest and the Cambridge Database already installed, and an available userid and password that you can use. Note its server-name. You will need this name later on2) Have available a local computer connected to the network and with ssh and Windows X11 clients installed.3) Log into the local computer.4) Start the X11 client.5) Type “hostname” to get the network name local-host of your computer.6) Type “xhost +server-name” that has ConQuest installed.7) Telnet or ssh server-name and log into the server with your assigned or guest

userid.8) Type “setenv DISPLAY local-host.weizmannn.ac.il:0.0”9) Type “cq”(You type items in blue as is, and replace items in green by the actual values.)

Notes1) If you would like to license ConQuest on an additional Unix computer, please contact Michal Harel, phone 2647. These licenses are quite expensive.2) Ask your system manager (Vadim of Structural Biology, or the Biological Services Computer Unit) to set it up for you. Have him see how in the slide notes below.3) You can also license the program on a Windows computer.

This is the main ConQuest window.To enter a search fragment, press “Draw”in the upper left.

We are now starting to draw in the search structurewithout hydrogens. Note on the left that we are in“DRAW” mode. On the bottom we can select theelement type (Hit “More…” for a periodic table.)and the bond type (Single, Double, Triple, Aromatic,Pi, Delocalized, etc). It is also possible to select anylist or group of element or bond types, meaning to allow any of the listed types to be selected.It is also possible to attach simple, common functionalGroups by hitting “Groups…” or “Templates…”.

To modify the structure after you have drawn it,select “EDIT” mode on the left and select the atomor bond you wish to modify with the right mousebutton. Besides changing the atom or bond type, you can also specify the exact or minimum number of bonded atoms or the whether the bond is part of a cyclic structure (2-D Constraints).To delete unwanted atoms or bonds, select “Erase”on the left and select the unwanted items.

To include or attach rings, select the ring type you want inthe lower left and click on an atom to attach, or bond to fuse.For any size ring with any kind of bond, select “RingMaker”.

Among the Atom and Bond Properties you can Change bySelecting with the Right Mouse Button or Atom or Bonds Menu:* Element or Bond Type* Exact number of bonded hydrogens* Exact number of bonded atoms* Whether atom or bond is part of a cyclic or non-cyclic structure

By selecting “Add 3D” and then some atoms, you can add:* 2 Atoms, you can add a distance constraint or vector.* More than 2 atoms, you can add a plane or centroid.* 3 or 4 Atoms, you can add an angle or torsional constraint.After selecting Define, by then selecting selecting Options, you can set therange of values and change the name for the given constraint or geom. item.

By selecting an atom and centroid or 2 centroids, you can set a distanceconstraint between them (eg. a centroid acts like a dummy atom).By selecting 2 vectors or planes, or a vector and plane, you can set an angleconstraint between them. Use torsion constraints to control tabulation to therange -180 to 180 deg. or 0 to 360 deg.For angles and torsions you can apply a trig function.After defining an item or if you make a mistake, select reset at the bottom.By selecting Options under the 3D menu in the Draw screen, you can eliminateduplicate and/or enantiomeric search fragments from the search results.

By hitting “ADD 3D” on the left, you can add 3-D constraintsto your search. Besides constraininginteratomic distances and angles, youcan also define vectors, centroids, planesand dummy atoms, and make constraintswith these entities.

This is our final search structure.

Besides searching using structural fragments, ConQuest, like the earlier Quest, allows you to search based on compound name, author, bibliogrphic (journal) information,chemical formula and/or crystallographic data. You can access these options by pressing the appropriate buttons on the left hand side under “Build Queries”. You can even set up additional search fragments under “Draw”, and use any or all of these search items to construct your final search question.

When all the search items are ready for searching, but sure to select all those you want to include in your search by checking the appropriate boxes. Then select the “Combine Queries” tab on the top. Place the search questions into the appropriate category boxes on the left for logical AND (search item must be present in each hit), logical OR (only one of the items need to be present) or logical NOT (item must NOT be present), and hit the “Search” button on the lower left. The “Manage Hitlists” tab on the top will allow you to combine or collate together the results of more than one search.

You reach this window after selecting “Search” from thepopup window you get from any of the options on the left.

You must be sure that these boxes are checked for allquery items that you want to include in your search. Thenselect “Combine Queries”, circled above, to construct asearch question using these items. Or simply select“Search” to find all entries that satisfy all search queries.

Copies of each of the query boxes above havebeen dragged into the appropriate boolean logicboxes to the left. When ready to run the search,hit “Search” on the lower left.

You can select a number of filters to restrict your search on the right. When you areready to search, select “Start Search” on the lower left.

To save your search template to use another time, in the “File” menu on the upper right of the Draw window, select “Save Template”. To restore, select “Load Template”.

When the search is finished, the “View Results” window opens. On the left areviewing options, which let you choose to display the molecular structures(default) or textual bibliogrographical, chemical or crystallographic informationin the central viewing window. Along the right is a list of REFCODES that all fitthe search criteria. You can select which entry to display by clicking on itsREFCODE.

To save the results of your search, select “Save Search” under “File”, and save as a .cqs file. By selecting “Export Entries as…”, you can also export the output coordinates in a variety of formats, including CIF (crystallogrpahic international standard format), PDB, MOL2, SHELLX RES and even the journal reference listings in EndNote format (.tsv file),. CIF (or RES) formats are recommended for use with the Mercury viewing program (described below), and PDB (or maybe MOL2) for use with viewers outside the Cambridge Database system.

Mercury is a free crystal structure viewing program that you can run from the same server as ConQuest, or you can download it from the Cambridge site athttp://www.ccdc.cam.ac.uk/. There are versions for Unix/Linux, Windows and Mac OSX.

It can handle multiple-entry CIF and RES files very nicely, and even readsConQuest .cqs files. To run standalone, type “mercury <file_name>”, wherethe optional <file_name> is the name of the file you want to open.You can even open Mercury (and Vista) from inside ConQuest itself.

Among the specialized features that it supports are the ability to view, looking down a crystallographic unit cell axis a, b or c, and displaying symmetry-related structures within the unit cell. It can read and write PDB, MOL2, CIF and SHELLX RES files, and can also write a PNG graphic file of the molecular display, which you can use in publications and presentations.Mercury handles multiple-entry files very nicely, by displaying a single entry at a time. To indicate which entry to display, select from the list on the right side.

Mercury

If your search included 3-D geometric constraints, you can obtain the summarystatistics by selecting under the “File” menu the item “Export Parameters and Data”. In the resulting popup box, you can save the data in a .tab file for Vista, a spreadsheet file for Excel, or a plain ascii format (.sum file) like the old quest used to do.

Vista is a program to analize summary statistics from 3-D geometric constraint searches. Besides providing a spreadsheet, it lets you make a histogramic distribution for any particular constraint, by selecting the appropriate spreadsheet column header, and then the “Histogram” button on the right. You can also make a scatter plot to compare the correlation of two constraints by selecting both headers and then buttom “Scattergram”.You can modify the plot styles and output them into PostScript format.

The 2 parameters from Test number 1 will now be tabulated

Nfrag Refcode DIST1 ANG1 1 ABEBUE 3.092 77.241 2 ABEBUE 3.092 77.241 3 ABOMOT 3.050 76.080 4 ACENEB 3.313 72.182 . . . . . . 214 CPIPLA 3.307 83.756 215 CPMCSI 3.598 75.283 216 CTPAZO 3.324 75.715 217 CTPAZO 3.342 70.054 Nent 120 Nobs 217 217 Mean 3.232 77.332 SDSample .166 8.158 SDMean .011 .554 Minimum 3.011 60.465 Maximum 3.700 89.833

In the summary statistics, note that the number of observations is generally largerthan the number of entries, because many entries have more than one represen-tation of the search fragment in the structure.

Scatter Plot

On-Line Help and Documentation

All the Cambridge Database programs come with extensive on-line help:1) Under the Help menu of the respective programs (upper right for Conquest and Mercury, including user-manual and tutorials), and lower right for Vista. Context sensitive - it will bring up the help material relating to the task you are trying to do.On-line copies of the documentation files can be found:2) in directory $CSD/docs/, while logged onto the server.3) at URL http://www.weizmann.ac.il/~cffelder/weiz/csd.html, at the Weizmann Institute.4) on the Cambridge home page at http://www.ccdc.cam.ac.uk/.

ConQuest and Mercury have many additional features, and there are several additionalprograms and capabilities in the Cambridge Database system, that are not included in this introductory presentation. You can find out about these by examining the on-line help and Cambridge Web Home Page.

We would like to thank:

The CCDC - for such a wonderful database and nice tools to access it.

Israel Council for Higher Education - for providing the funding for Israeli

universities to acquire and maintain this database, especially during these hard

times of major budgetary cutbacks.

Michal Harel - for her work to make sure the database is kept up to date and

needed licenses are obtained, and distributing the database materials to the

other Israeli universities

Vadim Neporent, Marilyn Safran, Irit Orr and Michael Green - for installing

the database on the Structural Biology and Bioinformatics/Biological Services

servers.

When citing work done using the Cambridge database in publications, you should

cite: “The Cambridge Structural Database: a quarter of a million crystal structures

and rising.” F.H.Allen Acta Cryst. B58, 380-388, 2002.