CDK Workshop 2009
of 17
-
Upload
asad-rahman -
Category
Documents
-
view
220 -
download
0
Transcript of CDK Workshop 2009
-
8/14/2019 CDK Workshop 2009
1/17
EBI is an Outstation of the Euro ean Molecular Biolo Laborator .
Syed Asad RahmanE-mail:[email protected]
Small molecules and reaction mechanism -Rewiring the enzyme space
04/21/2009
CDKWS- 2009
-
8/14/2019 CDK Workshop 2009
2/17
Overview
Understanding Metabolic Networks
Shortest path based conversion of substrate to product
Challenges and some meaningful solution
Pathway Hunter Tool (PHT)
Small Molecule similarity and its impact
Fingerprint vs Maximum Common Subgraph
SMSD (Small Molecule Subgraph Detector)
EC classification
Do the represent the bonds of Life or are they like computer IP address?
A step towards reaction homologues and its impact on EC classification
Transition state analogues
ERI (Enzyme Reaction Information)-Toolkit
-
8/14/2019 CDK Workshop 2009
3/17
Enzyme and reaction
E1 E2
5
1
2
51
1
2
2
3
3
-
8/14/2019 CDK Workshop 2009
4/17
-
8/14/2019 CDK Workshop 2009
5/17
Copyright restrictions may apply.
Rahman, S. A. et al. Bioinformatics 2005 21:1189-1193;doi:10.1093/bioinformatics/bti116
This figure exemplifies the problem of finding a validshortest path in the biochemical network
-
8/14/2019 CDK Workshop 2009
6/17
Copyright restrictions may apply.
Rahman, S. A. et al. Bioinformatics 2005 21:1189-1193;doi:10.1093/bioinformatics/bti116
Mapping Reactant and Product
Understanding patterns in reactions
Pathway Hunter Tool (PHT) A Platform for Metabolic Network Analysisand Potential Drug Targeting (PhD Thesis 2006)
http://kups.ub.uni-koeln.de/volltexte/2008/2450/
-
8/14/2019 CDK Workshop 2009
7/17
Connectivity Analysis: MetabolicCentric View
Google: Pathway Hunter Tool (PHT)
-
8/14/2019 CDK Workshop 2009
8/17
Tracing Atom(s) in the Pathway
ARM (http://www.metabolome.jp) PHT (http://pht.tu-bs.de/PHT/)
-
8/14/2019 CDK Workshop 2009
9/17
SIMILARITY SEARCH
Small Molecule Similarity
Reaction Similarity
-
8/14/2019 CDK Workshop 2009
10/17
Matching Chemical Moieties
Index of pattern matching Similarity (i.e. Tanimoto co-efficient)
Distance (i.e. Euclidean )
Finding similar molecules (i.e. substructure) MCS (Maximum common subgraph)
+ Very good for substructure search + Pinpoints the common patterns
- Computation exhaustive
Fingerprints (Descriptors of chemical moieties)
+ Fast and descriptor depended
+ Very good for reporting overall similarity and size of themolecule
- Cant map the matched patterns on the query molecule
-
8/14/2019 CDK Workshop 2009
11/17
Maximum Common Subgraph (MCS)
-
8/14/2019 CDK Workshop 2009
12/17
Few words about CDK MCS
Its very fast when two molecules are very similar!Except
MICS (Maximum Common Induced Edges), hence treatscyclopropane and Isobutane as similar molecules
Rings structures differ at non-ring sites
Ranking the MCS solutions
-
8/14/2019 CDK Workshop 2009
13/17
SMALL MOLECULE SUBGRAPHDETECTOR (SMSD)
Introducing a new Maximum Common Subgraph (MCS) calculationsoftware
http://www.ebi.ac.uk/thornton-srv/software/SMSD/
Google: SMSD + EBI
OR
http://www.ebi.ac.uk/thornton-srv/software/SMSD/cdkws2009.zip
-
8/14/2019 CDK Workshop 2009
14/17
MCS vs. SMSD
-
8/14/2019 CDK Workshop 2009
15/17
Fingerprint vs. SMSD (~50,000 pairwise comparison)
Tanimoto score = ~ 0.50 as 99 percentile of the data is covered~ 0.77 as 99.9 percentile of the data is covered
-
8/14/2019 CDK Workshop 2009
16/17
Acknowledgement
Franz Fenninger Dr. Lorenzo Baldacci
Dr. Gemma L. Holliday
Dr. Kazuto Yamazaki Dr. Matthew Bashton
Special thanks to CDK development team
Chemistry Development Kit (CDK) Chemaxon Open Babel
Prof. Janet M. Thornton Prof. R. Schrader
Prof. D. Schomburg
-
8/14/2019 CDK Workshop 2009
17/17
THANK YOU!
Syed Asad Rahman
E-mail: [email protected]
mailto:[email protected]:[email protected]
