This document summarizes improvements to ChemAxon's Maximum Common Substructure (MCS) search module. The new module has improved accuracy and run time, reduced memory usage, and reduced fragmentation compared to previous versions. Extensive tests show major improvements in these areas, including faster running times (e.g. from 20 minutes to 2.5 seconds on difficult structures), fewer fragments identified, and identification of more common bonds. Examples are provided to illustrate the improvements.

1. The Next Generation of
MCS Search at ChemAxon
Péter Englert

2. How similar are two molecules?
Method 1
0.71
Method 2
0.47
...
What do these numbers mean?
Method X
0.YZ

3. Structural Similarity
What do these molecules have in common?
Resulting Tanimoto similarity: 0.615
Similar property principle

4. A more complicated example

5. A more complicated example

6. Maximum Common Substructure
• Many applications
‐ Similarity Search
‐ Clustering
‐ Reaction mapping
‐ Molecule alignment
• A complex problem
‐ Solution often approximated

7. ChemAxon solutions
• 2004, JChem 2.3
‐ Backtracking algorithm
‐ Connected MCS only
• 2010, JChem 5.4
‐ Efficient heuristics
‐ Max-clique search based
• 2013, JChem 6.0
‐ Improved MCS module

8. The new MCS module
• Improved accuracy and run time
• Reduced memory usage
• Reduced fragmentation
• Many features
‐ Connected/disconnected
‐ Generic atom/bond handling
‐ Multiple results
‐ Ring matching (JChem 6.1)

9. Applications – 3D Alignment

10. Applications – Reaction Mapping

11. Applications – Library MCS

12. Improvements
• Better accuracy
• Improved running time
• Reduced memory usage
How much improvement?
Major improvements

13. Accuracy

14. Running time

15. Extensive tests

16. Memory usage
Tested on “hard” cases,
graphene-like structures

17. Examples
Result: 47 bonds, 1 fragment
~20 minutes
connected
JChem 2.3

18. Examples
Result: 83 bonds, 8 fragments
~2.5 seconds
fragmented
JChem 5.12

19. Examples
~0.2 seconds
optimal
Result: 92 bonds, 2 fragments
JChem 6.0

20. Examples
JChem 5.12
JChem 6.0
Reduced
fragmentation
7 fragments
3 fragments
query target
query target

21. Examples
JChem 5.12
JChem 6.0
22 bonds
92 bonds
query target
query target
Connected mode
improvement

22. ExamplesJChem 5.12
JChem 6.0
query target
query target
Goodbye
example

23. Summary
We have substantially improved our MCS solution
based on feedback from the previous versions
Acknowledgements:
Thank you for your
kind attention!
• JChem Base team
• Péter Kovács
• Miklós Vargyas