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.
Then you will see the search results:
Then you will see the search results:
Learn more about how to use chime: Video 1 (1,MB), Video 2 (3,7 MB)
CAS-Search
Then you will see the search results:
Chemical Name Search
Then you will see the search results:
Then you will see the search results:
Then you will see the search results:
Search for a Name of Substance
Then you will see the search results:
Then you will see the search results:
A direct superposition can also be performed after the compound search:
System Requirements for MDLŽ Chime:
PC:
Software: for Chime 2.6 SP5
- Windows XP with Microsoft Internet Explorer 6.0, and Netscape Communicator 4.75, 4.79
- Windows 2000 with Microsoft Internet Explorer 6.0, 5.5 SP2, and Netscape Communicator 4.75, 4.79
- Windows NT with Microsoft Internet Explorer 6.0, 5.5 SP2, and Netscape Communicator 4.75, 4.79
Hardware:
- Pentium class recommended
- 64 MB or more recommended
- 800 x 600 resolution or better recommended
Macintosh:
Software: for Chime 2.6 SP5
- Mac OS 9.0 with Netscape Communicator 4.75
- Mac OS 8.6 with Netscape Communicator 4.75
Hardware:
- Power PC required
- 32 MB or more recommended
- 800 x 600 or better recommended
- Connectix Ramdoubler is recommended if you have less than
32 MB of physical RAM.
You need to increase the memory used by Netscape to 15,000 K.
For more detailed information see MDLŽ Chime.
save two superimposed structures
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). "
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.
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.
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.
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).