msdmotif 1 adel golovin protein site and motif search biosapiense network of excellence
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MSDmotif 1
Adel Golovin
Protein Site and Motif search
Biosapiense network of excellence
MSDmotif 2
Overview
crystallographer
biochemistry Ph.d students
Pharma research ScientistOracle
Service Database
tomcatJ2EE application
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Search options
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Search example
1nio
+ Where N covalently binds sugar:
Super-secondary structure
Strand – <= 5 residues loop – Strand
+ N Glycosylation pattern N{P}[ST]{P}
+ 2-3 residues gap
150.000 coordinate entries
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Search results
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Binding statistics
Molecule binding
Pair binding
Motif binding
3D Environment?
•Chemical fragments
•Main/Side chain
•Plane interactions
•Stats on a family
•RR calculation
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Data retrieval
Chemical search PDB/CIF files with ligands and those 4.2 Å environment
Web Service XML request eFamily XML
Statistics in text files
Sequence alignment files
Distributed Annotation System (DAS)
HTTP URL request DAS XML
HTTP request text files, XML, PDB,CIF,ALN…
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Approach• Where to start?• Results presentation?
See: help->examples
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Ligand approachStaurosporine
Kinase inhibitorLigand fragment binding statistics
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Molecule binding interface
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Protein sequence approachTyrosine protein
kinases specific active-site signature:
[LIVMFYC]-{A}-[HY]-x-D-[LIVMFY]-[RSTAC]-{D}-{PF}-N-[LIVMFYC](3)
Motif binding statistcs
Ligand fragments
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Motif binding statistics
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Protein sequence approach 2• Tyrosine protein
kinases specific active-site signature:
• [LIVMFYC]-{A}-[HY]-x-D-[LIVMFY]-[RSTAC]-{D}-{PF}-N-[LIVMFYC](3)
Search 3D alignment
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Protein structure approach3D fragment Search Sequence
pattern
φ/ψ sequence
-156/-155,-103/17,-134/161
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Protein structure approach 2• Sample motif from a
PDB entry
• Complete graph search by CA or end of side chain positions
• 3D alignment of the hits
S
CA
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Computer Aided Drug Design
Drug Bioavailabilitybioactivity
Physicochemicalmodelling
Drug Leadoptimisation
Similaritysearch
Homology modelling
Sequenceanalysis
vHTS
CADD
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Computer Aided Drug Design
Modelling
PredictionSearch
Alignment
Analysis
• A good prototype is often better than a best model• Sequence and 3D multiple alignment largely improve model quality
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Availabilitywww.ebi.ac.uk/msd-srv/msdmotif/
MSD: www.ebi.ac.uk/msd GN
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lic license
golovin@
ebi.ac.u
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