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TitleMogul User Guide and Tutorials
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Page 1

Mogul User Guide and Tutorials

2016 CSDS Release

Copyright © 2015 Cambridge Crystallographic Data Centre

Registered Charity No 800579

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ii Mogul User Guide and Tutorials

Conditions of Use

The Cambridge Structural Database System (CSD System) comprising all or some of the
following:

ConQuest, Quest, PreQuest, deCIFer, Mercury, (Mercury CSD and CSD-Materials [formerly
known as the Solid Form or Materials module of Mercury], Mercury DASH), Mogul, IsoStar,
DASH, SuperStar, web accessible CSD tools and services, WebCSD, CSD Java sketcher, CSD
data file, CSD-UNITY, CSD-MDL, CSD-SDfile, CSD data updates, sub files derived from the
foregoing data files, documentation and command procedures, test versions of any existing
or new program, code, tool, data files, sub-files, documentation or command procedures
which may be available from time to time (each individually a Component) is a database and
copyright work belonging to the Cambridge Crystallographic Data Centre (CCDC) and its
licensors and all rights are protected. Use of the CSD System is permitted solely in
accordance with a valid Licence of Access Agreement or Products Licence and Support
Agreement and all Components included are proprietary. When a Component is supplied
independently of the CSD System its use is subject to the conditions of the separate licence.
All persons accessing the CSD System or its Components should make themselves aware of
the conditions contained in the Licence of Access Agreement or Products Licence and
Support Agreement or the relevant licence.

In particular:

The CSD System and its Components are licensed subject to a time limit for use by a
specified organisation at a specified location.

The CSD System and its Components are to be treated as confidential and may NOT
be disclosed or redistributed in any form, in whole or in part, to any third party.

Software or data derived from or developed using the CSD System may not be
distributed without prior written approval of the CCDC. Such prior approval is also
needed for joint projects between academic and for-profit organisations involving
use of the CSD System.

The CSD System and its Components may be used for scientific research, including
the design of novel compounds. Results may be published in the scientific literature,
but each such publication must include an appropriate citation as indicated in the
Schedule to the Licence of Access Agreement or Products Licence and Support
Agreement and on the CCDC website.

No representations, warranties, or liabilities are expressed or implied in the supply
of the CSD System or its Components by CCDC, its servants or agents, except where
such exclusion or limitation is prohibited, void or unenforceable under governing
law.

Licences may be obtained from:

Cambridge Crystallographic Data Centre
12 Union Road
Cambridge CB2 1EZ, United Kingdom

Web: http://www.ccdc.cam.ac.uk
Telephone: +44-1223-336408
Email: [email protected]

(UNITY is a product of Certara and MDL is a registered trademark of BIOVIA)

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9.5 Printing a Histogram
To print the histogram currently displayed within the Results and analysis pane, together
with its associated summary statistics, either:

 Select File from the top-level menu, followed by Print... from the resulting drop-
down menu.

 Click the right-hand mouse button anywhere within the histogram display area, then
select Print... from the resulting menu.

To change the display style of a histogram right-click in the histogram display area, and from
the resulting menu select the required option (Font..., Selected Colour..., Deselected
Colour..., Background Colour...).

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Mogul User Guide and Tutorials 55

10 The Mogul Instruction File

10.1 Using an Instruction File with Mogul
A Mogul instruction file allows Mogul to be run automatically in batch mode and provides a
way of integrating Mogul with other applications. To start Mogul using an instruction file,
issue the following command:

Windows:
<INSTALLDIR>\mogul.exe -ins <instruction_file>

UNIX:
<INSTALLDIR>/bin/mogul -ins <instruction_file>

where <INSTALLDIR> is the Mogul installation directory and <instruction_file> is
the name of the Mogul instruction file. For example:

Windows:
C:\Program Files (x86)\CCDC\CSD_2016\Mogul 1.8\mogul.exe -ins
instructions.txt

UNIX:
/usr/local/cambridge/mogul/bin/mogul -ins instructions.txt

On Windows, it may be possible to identify the location of the most recent version of
mogul.exe via the Windows registry. The following registry keys will have been written by
the Mogul Software installer in either HKEY_LOCAL_MACHINE or HKEY_CURRENT_USER:
Software\CCDC\MogulLatestVersion = <ver> (where <ver> = 1.2 for example)
Software\CCDC\Mogul\<ver>\Executable = <INSTALLDIR>\mogul.exe

10.2 File Locations
Mogul should automatically pick up the locations of data and other files. If it does not then
these can be provided via additional command line options as follows:

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Mogul User Guide and Tutorials 115

common in six membered rings. Perhaps this indicates that this ligand model is a
better one?

 Try to find more hits. Very few hits of relevance 1.0 are found, which might be a
significant observation.

8. Finding more information: analysing the torsions.

 We will again examine whether other geometrical features look odd. Go back to
the Build query window and select All fragments.

 Toggle on All torsion fragments and ensure all the other options are toggled off.
Click on Search.

 Again sort the All fragments: Results table by d(min). Examine the torsions
represented by the top two rows on the query structure. Two torsions are
represented, both close to the piperidine fragment.

 Look also at the histograms for these torsions. The query values are well away
from the CSD distribution. Does this then mean that the model is bad after all?

9. A hypothesis

 The 1hak_ligand_A.mol2 structure is very likely to be a bad model. The ring
conformation is clearly highly unusual. What about the model
1hak_ligand_B.mol2 however?

 There is a clue to the answer in that very few examples of relevance 1.0 were
found for model B. Relevance in rings depends on three factors, number of
substituents on each ring atom, size (small or large) of each ring atom
substituent; and relative stereochemistry. The piperidine ring is substituted only
twice, in the 1 and 4 positions and the substituents themselves are both
considered ’small’ (because the atom of each substituent adjacent to the ring
only has at most one additional heavy atom attached). It is unlikely that other
similar examples cannot be found in the CSD, and in fact we know such
examples exist because 9 examples with relevance 1.0 were found for the search

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on 1hak_ligand_A.mol2. Therefore it must be the relative stereochemistry of
the two ring substituents that is the unusual factor, and which forces the ring
search to generalise and get other hits.

 Examination of the piperidine ring in 1hak_ligand_B.mol2 shows both
substituents to be UP (or DOWN). Why is this so rare in a 1,4 substituted
piperidine?

 The answer lies in the stereochemical preferences of substituted saturated six
membered rings. So called axial substitutions where the substituent points
vertically up perpendicular to a plane through the ring (chair conformation
assumed) are less stable (because they make more close contacts to ring Hs)
than equatorial substituents which, as their name suggests, come off the sides
of the ring (see diagram). The benzyl group in Model B coming off the a
piperidine ring carbon, is in an axial position. The substituent off the nitrogen
atom is in the equatorial position. This conformation for the piperidine ring is
unusual because the nitrogen in similar compounds is usually able to invert itself
(umbrella inversion) so that its substituent is axial. The six membered ring can
then also invert by a process called intra-chair conversion and in this process
both axial ring substituents can then take up the much more stable equatorial
position. Consequently we see that the piperidine ring in Model B still contains
significant strain, despite having a common chair conformation, and that this
strain is at least in principle resolvable by adopting an alternative conformer.

 We see now that both model A and model B are highly strained structures. A full
analysis would require us to look at the electron densities in both structures.
However, even without that, a working hypothesis might be that the
crystallographic refinement of both ligand models is not as good as it could be
and that, if the crystallographer could have used alternative starting models for
each ligand structure, it might have been possible to generate models with good
fit to the electron density, which contained low strain piperidine conformations,
each a chair form with two equatorial substituents.

This ends the tutorial.

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