FAQ

FAQ

 

1.    I know a name of a compound e.g. Aspirin and I'm looking for the...

2.    I know the ATC - Code or CAS - Number of a compound and I'm looking for the ...

3.    How can I do a 2D search against the database with 85% similarity?

4.    How can I perform a 3D Superposition?

5.    What are the system requirements for MDLŽ Chime?

6.    How can I save a 3D structure?

7.    How can I save two superimposed structures?

8.    How long takes a 3D superposition?

9.    How are the conformers generated?   

10.    I have a lot of rotatable bonds, but only a few conformers. What could be the reason?

11.    I have a lot of conformers, but only a small number of rotatable bonds. Can this be reasonable?

12.    I noticed differences between the structure that is displayed after a search and the structure that is shown by the conformers.


ATC-Search

 

 

Then you will see the search results:

 

 

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3D Structure Search

 

 

 

Then you will see the search results:

 

 

Save 3D structure



Learn more about how to use chime: Video 1 (1,MB),  Video 2 (3,7 MB)

 

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CAS-Search

 

 

Then you will see the search results:

 

 

 

 

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Chemical Name Search

 

 

Then you will see the search results:

 

 

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Molecular Formula Search

 

 

Then you will see the search results:

 

 

 

 

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Mixture Name Search 

 

 

Then you will see the search results:

 

 

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Search for a Name of Substance

 

 

 

Then you will see the search results:

 

 

 

 

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2D Similarity Search

 

 

Then you will see the search results:

 

 

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3D Superposition

 

Then you will see the results:

 

 

A direct superposition can also be performed  after the compound search:

 

 


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System Requirements

 

System Requirements for MDLŽ Chime:

PC:

Software: for Chime 2.6 SP5

 

Hardware:

 

Macintosh:

Software: for Chime 2.6 SP5

 

Hardware:

 

For more detailed information see MDLŽ Chime.

 

 

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save two superimposed structures

 

 

 

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duration of a  3D superposition

 

How long takes a 3D superposition?

 

"It depends on the server loading time and the number of conformers for both compounds (max. 20-30s). "

 

 

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Generation of conformers

 

We generated the conformers with "Catalyst 4.7", a software from Accelrys. This program uses a poling algorithm to promote conformational variation. The poling algorithm helps to eliminate much of the redundancy in conformer generation and improves the coverage of conformational space. To remove similar conformers Catalyst screens the generated conformers to see if any two conformers are within the RMS tolerance. The RMS tolerance is computed as:

RMS_TOL = 0.1 + c * sqrt ( 1 + Nrot )

where C is a scaling constant and Nrot  is the number of rotatable single bonds (allowing the tolerance to scale with molecular flexibility). All conformers in the Super Drug Database are generated with a value of  0.15 for C. For structures with more than 60 rotatable bonds we normally assume that these are proteins or long peptides. For these compounds we did not generate conformers, because only crystallographically (or NMR) determined structures can deliver reliable structures. One example for this case is the human Insulin. Here we have taken the structural data from the Protein Data Bank (PDB) (PDB-code: 1BEN).

Catalyst can use two different methods of conformer generation: FAST and BEST. The BEST-method provides improved conformational coverage relative to the FAST method. One improvement is a more rigorous energy minimization in both torsional and cartesian space. For the Super Drug Database we used the BEST-method.

Another parameter of Catalyst is the maximum energy for each conformer. We take a threshold of 20 kcal/mol as a relative maximum energy.

Catalyst allows to define the maximum number of conformers for each compound. Values from zero until open end are possible. We generated all conformers with a maximal number of 100 conformers for each substance.

In Catalyst the chiral centers can be set as absolute (the stereo center is known) or unknown. This has a direct impact on the conformer-generation routines, because if a stereocenter is marked as unknown it can be either R or S. Catalyst is able to read the chirality flag in the MDL MOL files. For our conformers we set the stereocenters to absolute, provided that stereochemistry is known.

 

If you want to get more information about the conformer generation you can have a look at this description from Accelrys.

 

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Many rotatable bonds, only a few conformers

 

In some cases the compound has a lot of rotatable bonds, but only a few conformers. This can occur if the single bonds are in a large ring system. An example for this case is Vancomycin (CAS: 1404-90-6).

Catalyst performs a symmetry check of the conformers. When the symmetry difference between two conformers is too low, these conformers also will be omitted.

 

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Many conformers, only a few rotatable bonds

 

In some cases the compound may have many conformers, but only a few rotatable bonds.  This depends on the isomerism (cis-trans isomerism, unknown chirality or stereoisomerism) of the structure. Indigo carmine (CAS: 860-22-0) is a good example for cis-trans-isomerism. Also see Lindane (CAS:58-89-9) for an example with no rotatable bonds but with four conformers and stereochemistry is not set.

Catalyst performs a symmetry check of the conformers. When the symmetry difference between two conformers is too low, these conformers will be omitted.
 

 

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Differences between display styles

 

The structure which is displayed after a search is displayed by using chimestrings. These structures which are shown in search results may contain ions and other additives (which are ignored during the conformer generation process). The structures of the conformers are displayed using the mol-files generated by Catalyst. If you are interested in a 3D structure for simulation purposes etc. please use the structure accessible via the "conformer" button (Full Info or Statistics).