cdk workshop 2009
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EBI is an Outstation of the Euro ean Molecular Biolo Laborator .
Syed Asad RahmanE-mail:asad@ebi.ac.uk
Small molecules and reaction mechanism -Rewiring the enzyme space
04/21/2009
CDKWS- 2009
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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
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Enzyme and reaction
E1 E2
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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
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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/
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Connectivity Analysis: MetabolicCentric View
Google: Pathway Hunter Tool (PHT)
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Tracing Atom(s) in the Pathway
ARM (http://www.metabolome.jp) PHT (http://pht.tu-bs.de/PHT/)
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SIMILARITY SEARCH
Small Molecule Similarity
Reaction Similarity
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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
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Maximum Common Subgraph (MCS)
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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
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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
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MCS vs. SMSD
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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
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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
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THANK YOU!
Syed Asad Rahman
E-mail: asad@ebi.ac.uk
mailto:asad@ebi.ac.ukmailto:asad@ebi.ac.uk
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