CSD hands-on exercises 2010

CSDS Hands-on Tutorials at CSC Workshop
9th November 2010
For practical help with the CSC environment, see:
http://www.csc.fi/chem -> Introduction
For more in-depth help (and more tutorials) with the Cambridge Crystallographic
Database System, see individual Help pages (choose help in each module) or the
CSDS web page: http://www.ccdc.cam.ac.uk/
Note. The material (its origin) is copyrighted by CCDC. Don’t distribute without their
written permission.
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ConQuest: Basic Substructure Search
Objectives
To draw a chemical fragment (substructure).
To search the CSD for entries which contain the fragment.
To obtain a list of journal references for the hit entries.
Transfer the results to Mercury.
Steps Required
Draw the fragment in the substructure drawing window.
Start the search.
Decide which hit entries to keep.
Write out the journal references.
The Example
The tutorial explains how to search for the following fragment:
where 7A = F, Cl, Br or I.
Step by step instructions
1. Start ConQuest and hit the Draw button to open the Draw window.
In Hippu give: module load ccdc and then start ConQuest with cq
2. Draw a chain of atoms.
Move the cursor into the white drawing area, press the left-hand mouse button, and
move the mouse while keeping the button depressed. Release the mouse button
and you should have drawn a C-C bond. Keep the cursor where it is, i.e. on one of
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the carbon atoms. Press the left-hand button again and draw a second bond, and
then a third to produce:
If you make a mistake (here, or elsewhere in the drawing area), click on Edit (in the
top-level menu) and then Undo (or ctrl-z as shortcut).
3. Add the carbonyl group.
Select O from the list of common elements at the bottom of the Draw window.
Click on the button next to the word Bond at the bottom of the Draw window and
change the bond type from Single to Double.
Move the cursor back into the white area and draw a bond to the second carbon in
the chain. Since the current atom type is O and the current bond type is double, this
creates an O=C bond:
4. Create an acetoxy group.
O is the current element, so click on the first carbon in the chain to change it to an
oxygen:
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5. Create a halogen substituent.
Click with the right-hand mouse button on the carbon at the other end of the chain.
Select Element from the pull-down menu, followed by More from the next menu,
then Any Halogen.
The terminal carbon should now have changed to 7A (the symbol used in ConQuest
to denote the halogen group of elements).
6. The fragment is now drawn. Do the search.
Hit the Search button in the bottom right-hand corner of the drawing window. This
produces a pop-up window telling you which version of the CSD you are going to
search.
This window allows you to specify some filters. Click on 3D coordinates determined
to ensure that you will only find CSD entries for which 3D atomic positions are
available.
Hit Start Search.
7. Look at the results.
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As soon as you start the search, the ConQuest interface moves to the View Results
pane. After a few moments, the refcodes of hit structures start to appear in the list
on the right-hand side. Click on any structure to see its chemical diagram.
Click on the Detach Diagram button, this allows the 2D diagram to be shown in its
own window enabling the 2D diagram and any other results panes to be viewed
simultaneously. Now use the tabs (Author/Journal, Chemical, etc.) to see other
types of information.
Rather than allowing the search to go to completion, you can stop it by hitting the
Stop Search button in the bottom right-hand corner. The blue progress bar indicates
how much of the CSD has been searched so far. A pop-up menu asks if you really
wish to stop the search as it cannot be resumed once stopped.
8. View structures in 3D.
Click on the 3D Visualiser tab to see the currently selected structure in 3D.
Rotate the structure by moving the cursor in the 3D-display area while pressing on
the left-hand mouse button.
Change the display style by clicking anywhere in the 3D-display area with the righthand mouse button. Select Display Style from the pull-down menu, then select a
display style.
9. Suppress unwanted hits.
Suppose you don’t want to keep the first hit. Suppress it by clicking on the green tick
next to the refcode. The tick turns into a red cross. This structure will not be written
out in any files you export.
10. Writing out a file containing journal references.
Click on File in the top-level menu and select Export Entries as... from the pull-down
menu.
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Click on the file type bar and select TXT: Text representation from the pull-down
menu.
Turn the output off for everything except Bibliographic information (i.e. click in the
check-boxes so that only the one next to Bibliographic is coloured red).
Hit Save to save the file of journal references.
11. Transferring the hits to Mercury.
Mercury is an advanced crystal structure visualiser. To view the hits from this search
in Mercury hit Analyse Hitlist and select View in Mercury from the pull-down menu,
This ends the tutorial.
6
3D Substructure Search and VISTA
analysis
Objectives
•To draw a chemical fragment (substructure).
•To select only those entries which adopt a particular conformation.
•To tabulate some parameters involving derived objects (centroids, planes).
Steps Required
•Draw the fragment.
•Define centroids and planes.
•Define distances between the centroids, and angles between the planes.
•Define a torsion angle and specify that it must lie in a certain range.
•Run the search.
•Save the file of geometrical parameters.
The Example
•The tutorial explains how to search for the following fragment:
where the two central carbons are acyclic (not part of a ring) and are bonded to 1 or
2 hydrogen atoms. The two phenyl groups will be required to be cis (i.e. Cring-C-CCring torsion angle between –90 and +90 degrees). The following parameters will be
saved:
• Distance between the centroids of the phenyl rings.
• Angle between the planes of the phenyl rings.
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Step by step instructions
1. Start ConQuest and hit the Draw button to open the drawing window.
2.Draw the basic fragment.
Use the aromatic bond type for the ring bonds, not alternate double-single (you
will get the correct bond types automatically if you select the rings from the ring
•template area at the bottom left-hand corner of the Draw window):
3. Specify the central C atoms to be acyclic.
Select Atoms from the top-level menu, Cyclicity from the pull-down menu, and
Acyclic from the next menu.
Click on the two central carbon atoms:
• Hit Done in the Select Atoms pop-up.
4. Specify the number of attached hydrogens.
• Select Atoms from the top-level menu, Hydrogens from the next menu, and
Other... from the third menu.
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• Type 1,2 into the Hydrogen Count box and hit OK.
• Click on the two central carbon atoms:
• Hit Done.
5.Define the centroids of the phenyl rings.
• Click on the ADD 3D button.
• Click on all six atoms of one of the phenyl rings and hit the Define button next to
the word Centroid. This defines the centroid of the ring (named, by default, CENT1):
•Similarly, define the centroid of the other ring (named, by default, CENT2).
6. Define the ring planes in a similar way.
• Click on the six atoms of one of the rings and hit the Define button next to the
word Plane. By default, the plane is called PLN1.
• Repeat for the second ring (named, by default, PLN2).
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7. Define the distance between the centroids and the angle between the planes.
• Click on the names of the two centroids, CENT1 and CENT2, in the box headed
Defined Objects:
Then hit the Define button next to the word Distance. This specifies a parameter,
DIST1, which is the distance between the two ring centroids.
Similarly, click on PLN1 and PLN2 and Define the angle between these planes.
8. Constrain the search so that it will only find structures in which the phenyl groups
are cis.
Click on the four atoms defining the conformation around the central C-C bond:
• Define the C-C-C-C torsion angle by hitting the Define button next to the word
Torsion.
• Hit the Options... button.
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• Type the required limits (From –90 to 90) into the 3D Limits and Options window.
The specified torsion angle range is displayed graphically:
• Hit OK in this window and then Done in the Geometric Parameters window.
9. Run the search.
• Hit Search, set the filters R factor <= 0.1, Not disordered, No errors and Not
polymeric, and then hit Start Search.
• View some of the hits in the 3D visualiser to confirm that the search is only finding
structures in which the phenyl rings are cis.
• Use the arrows on either side of the boxes labelled Param and Objects to control
whether or not distances, angles, centroid and planes are displayed.
10. Saving results
A file of the parameters you have defined can be saved by selecting File from the
top-level menu, then Export Parameters and Data from the pull-down menu. There
are many formats and possibilities in saving data.
11. Viewing results in Mercury
A fancier view is obtained with Mercury. You can transfer the hit structures and
parameters to Mercury with one click: Choose File -> View in Entries Mercury.
In Mercury you can, e.g. superimpose the structures based on your 3D search
criteria.
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12. Viewing results in VISTA
As it is difficult the get an idea of 400 hits by viewing them separately, there is a
handy option to quickly look at the statistics and spread of the search parameters by
using VISTA. This is done easily from the File menu: click the button View in VISTA
and accept the next popup.
Click once in the VISTA window to activate the interface. To have a look at the
correlation of the torsion angle and the distance between the phenyl ring
centroids, click at the column numbers and then click at the right side button
scatterogram.
You can get back to the VISTA front page with the red Return button at the top.
Try some of the other visualization tools too. Some of them require less or more
columns to become active.
The plot details can be changed at the right panel in the plot view. The plots can
be printed as postscript or captured from the screen (Prt Scr key).
This ends the tutorial.
12
Mogul Tutorial: Validating Molecular
Dimensions
Mogul is a library of intramolecular geometry and provides instant click of a button
access to geometrical distributions of bond lengths, valence angles, torsion angles,
and ring conformations. Uses include validation of newly determined crystal
structures, identification of unusual geometric features, and checking of
conformations generated by computational procedures.
Introduction
• Comparing the dimensions of a newly determined small-molecule crystal structure
with the bond lengths and angles of similar structures in the CSD is extremely useful
both as a check against refinement errors and to highlight unusual geometric
features.
• This tutorial demonstrates how to search on all bond and angle fragments in a
query molecule and shows how unusual or even suspect geometric features can be
readily identified.
Step by step instructions
1. Start mogul with the command mogul. Import the query structure:
• Click on the Load button in the Build query pane. In the resulting Load molecule
dialogue box, select cyclopropyl.mol2 from
/v/linux26_x86_64/appl/chem/ccdc/5.31/cambridge/examples/
mogul/tutorials and hit Open.
2. Search on all bond lengths and angles.
• An All fragments search will allow you to search for all valid bond lengths, valence
angles and/or torsion angles within your query molecule.
• Click on the All fragments... button on the left of the Build query screen. In the
resulting Search for all fragments pop-up, disable the All torsion fragments check-box
and ensure that both the All bond fragments and All angle fragments check-boxes are
selected.
• Hit Search to run the search.
3. Viewing the search results.
• The results from an All-fragments search are displayed (in spreadsheet format) in
a separate Allfragments search window.
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• Results for either bond length or valence angle fragments can be viewed by
clicking on the appropriate tab at the top of the All-fragments search window.
• Click on the Bond tab. Each bond fragment in the query structure is listed in the
spreadsheet together with the summary statistics for the corresponding Mogul
distribution.
4. Identifying unusual geometric features.
• For each bond fragment in the query structure statistics are given in the Allfragments search window, these include: number of observations, minimum,
maximum, mean, median, standard deviation, value in query and z-score.
• z-score is the absolute difference between observed and mean values of a
geometric parameter divided by the standard deviation of the Mogul distribution.
Therefore, a high z-score (e.g. >2.0) may indicate an unusual or even suspect
geometry within your query.
• The rows of a spreadsheet can be sorted according to the values in any of the
columns. Click on the z-score column header button to sort the rows by z-score.
• Notice that the C1-C2 bond length has a high z-score value (2.334). To investigate
this potentially suspect bond length further, display the search results for the C1-C2
bond fragment by clicking on the corresponding row in the spreadsheet.
• In the main Mogul window click on the Build query tab. The C1-C2 bond fragment
is directly attached to a cyclopropyl ring and is highlighted in the query structure.
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5. Analysing the results
• Click on the Results and analysis tab in the main Mogul window. The value of the
C1-C2 bond length in the query is superimposed in red on the histogram. This allows
for easy comparison with the geometric results obtained from Mogul.
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• When compared to similar structures in the CSD the C1-C2 bond in the query
structure appears to be unusually short (1.481 Å) and falls outside the main Mogul
distribution.
• However, there are a small number of observations in the histogram with a similar
value to that of the query structure.
• In order to inspect just these structures deselect all hits in the histogram by
clicking on the Deselect button, then highlight the three histogram bins located
around 1.48 Å using the horizontal bar located directly under the histogram:
• Click on the View structures tab and inspect the CSD entries that contribute to the
selected bins.
• Notice that for each hit structure the search fragment is also attached directly to a
cyclopropyl ring. Therefore, it might be reasonable to assume that the shortening of
the C1-C2 bond is a consequence of the cyclopropyl group and representative of this
type of structural motif (i.e. the C1-C2 bond length in the query structure is in fact
correct).
• In order to confirm this check some of the hit structures in the more populated
region of the distribution and satisfy yourself that these do not contain a cyclopropyl
group.
This ends the tutorial.
16
IsoStar Tutorial: Isoxazole and indole
hydrogen bonds
IsoStar is a library of intermolecular interactions. It is derived from data contained in
the CSD and the PDB. It features:
• Intermolecular contact information for nearly 350 central groups and over 45
contact groups.
• Contact distributions displayed as scatterplots or density surfaces.
• Theoretical data for selected model systems.
• A simple web browser interface.
Using IsoStar, Introduction
In this tutorial you will learn how to:
• access IsoStar at hippu.csc.fi using a web browser (this is aliased to isostar).
• navigate the IsoStar pages, to locate and display scatterplots for contacts between
isoxazole and various polar X-H groups in the CSD.
• manipulate the isoxazole scatterplots, using the IsoStar control window to display
only the shortest contacts, identify and display the CSD entries in which these
contacts are found and measure the contact distances.
• produce density surfaces from the isoxazole scatterplots and note the significant
features.
• locate and display scatterplots for interactions between indole and N-H groups in
the CSD and the PDB. Then manipulate these plots such that the underlying trends
are clear and note the
significant features.
Step by step instructions
1. Initialise CSD with module load ccdc and start IsoStar on hippu with the command
isostar
2. Selecting the system: Select Ligand, Ring systems, N, O, C, H only from the list of
central groups displayed on the left hand side of the IsoStar Home Page.
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3. Choose ligand. A list of ligand ring systems containing N, O, C and H is now
displayed in the main part of the browser window. Scroll down this list until you
locate isoxazole and click on the link to display the isoxazole contact tables.
4. Use the N-H hyperlink above the tables to move directly to the contact table for
N-H and click on the link for any NH in the CSD column to display the scatterplot.
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5. Manipulate view. The scatterplot is rotated using the left mouse button,
translated using the middle (scroll) mouse button and zoomed using the right mouse
button.
6. Undisplay long distance hits. Click the vdW overlaps button in the control
window to remove all contacts greater than the sum of van der Waals radii from the
scatterplot.
What does the scatterplot tell you about how N-H groups prefer to approach
isoxazole? Is this what you expected?
7. Control hits visibility. Using the UpperLimit slider bar, remove all but the shortest
one or two contacts from the scatterplot.
• Activate the Hyperlink checkbox above the scatterplot by clicking on it. This will
switch on hyperlinking.
• Select one of the contact groups still displayed in the scatterplot using the mouse.
• The selected contact will turn green, and the contact, as observed in the CSD, will
be displayed in the right hand side visualiser window.
• Note also that the tab in the Previous Files part of the IsoStar visualiser window
has changed from Scatterplots to Hyperlinks, and that the CSD refcode is given in
the CSD Identifier window.
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8. Measuring options. A number of options that allow further control over the
appearance of the contents of the visualiser window are available by right clicking
anywhere in the visualiser. It is also possible to measure distances, angles and
torsions via this menu. The contact distance in the hyperlink window can be
measured in the following way:
• Ensure the Hyperlink window is the active one either by clicking in the window
itself or by hitting the Current visualiser radio button.
• Right click in the window, and select Measure then Measure Distances from the
pull-down menu.
• Now determine the length of the N...H contact distance by clicking on both atoms
that are involved in the contact.
• Close the IsoStar viewer to return to the browser window that has the contact
group selection lists (File / Exit).
9. Compare to other hydrogen bond donors. Display the scatterplot for contacts
between isoxazole and any polar X-H in the CSD (this contact group is in the General
contact table).
• Select the Create/Edit button in the Contour Surfaces line. This will open a Contour
Surfaces window where it is possible to add contours to the scatterplot and
configure them.
• Blue contours will appear on the scatterplot. Level 25 implies that it is 25 times
more likely than random chance that a contact will occur within the blue contour.
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Now hide the scatterplot by dragging the upper limit all the way to the left.
How does this plot compare with the plot for N-H donors only? Is this what you
expected?
10. Looking at a new system. Close the IsoStar control window and return to the
browser.
11. New ligand/central group. Find the central group indole (see below; Ring
systems, N,C,H only).
12. Display scatterplots for the interactions between indole and any NH in the CSD
and in the PDB.
Compare the two plots. What are the differences?
13. Produce a density surface from the indole...any NH CSD scatterplot with the
default values. The blue contours can be hidden if required by de-activating the
tickbox under the Show column in the Contour Surfaces window. Contour Surfaces
window opens with the Create/Edit button.
What does the density surface tell you about interactions between indole N-H? Is
this what you expected?
This ends the tutorial.
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Mercury Tutorial: Slicing crystals
Objectives
Many interesting phenomena occur at the interface of two phases, like solid-liquid
interface. With Mercury it is easy to understand which crystal face (Miller plane)
corresponds to which macroscopic dimensions and how to generate such faces at
the molecular level. Mercury has a tool called Packing and Slicing (from Calculate
menu).
Steps / overall workflow
In this tutorial you create a small model system of some crystal structure where the
slab surface matches the one predicted to be prevalent also in the macroscopic
crystal.
Step by step instructions
1. Open Mercury and Choose some crystal structure (e.g. TETZOLO2)
Mercury starts in Hippu with mercury in the command prompt.
Write the refcode in the right hand side text box or choose your own structure
Click packing on from the lower left side.
Show close contacts by clicking the tick boxes at lower left side (H-bonds, Short
contact)
Expand some of the closest molecules by clicking at the + signs at the end of the
dashed bonds.
To undisplay single expanded molecules right click it and choose Delete this
molecule.
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2. Calculate -> BFDH-Morphology
3. Identify the major crystal face(s).
Is there a clear dominant surface? (Note that BFDH is a crude approximation in
predicting the crystal macroscopic morphology).
4. Choose the Slicing and Packing tool from Calculate menu, and Click on the Show
Slice tick box in the Slicing tool. Try different Miller (hkl) planes.
The slicing options are ordered according to their relative surface area. Did you
think of the same surface as the tool suggests as the dominant one?
You can fine tune the slab with the sliders (Depth, Area, Displacement) in the
slicing tool. A good model is thick enough to have all the important features and
wide enough to display the functionality that you have in mind for the actual
application. On the other hand computational load will place constraints at the
maximum size. Which groups are likely to be found at the crystal surface? Are
there any choice in your case?
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5. Save the model, once you are happy with it for use in another application.
Without closing the Slicing and Packing tool, click File -> Save As and choose e.g.
pdb (or any format that has the crystal axes information in it) note its name and
hit ok.
Have a look at the file with a text editor (or e.g. unix command less ), e.g. with
vmd. To do this in Hippu, in command prompt give:
module load vmd
vmd yourstructure.pdb
This ends the tutorial.
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