MSDmotif 1

Adel Golovin

Protein Site and Motif search

Biosapiense network of excellence

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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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