EMBL-EBI MSD motifwww.ebi.ac.uk/msd-srv/msdmotif

PDB: 1gci

Structure Annotation

and

Function Assignment with MSDmotif

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MSDmotif front options

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Small motifs

Alpha-Beta Motif Nest ST staple

11 motifs in total

Prof James Milner-White

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Small motif stats

Occurrence of amino-acids Correlation of side chain charge

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Small motif stats

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Small motifs – hit list from stats

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Small motifs – 3D alignment

ST-staple

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Small motifs viewing

LigandsCatalytic sites

ProSiteSmall motifs

“Group” menu item contains a list of presented in a PDB entry sites and motifs

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, search

Ideal for short loops search

PDB:1gci

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, search - continue

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, search - continue

PDB:1gciSubtilases family

PDB:1f5pGlobins family

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, search vs sequence search

Sequences found while search by , :

Subtilases family NNSIGVLDNTTGVLDNSIGVL

Globins familyIVDTGSV

Blast search for NNSIGVL

Diphtheria toxin family

SDSIGVL

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3D motif research

PDB 1e4m has the small motif - Asx turn of residues 65-67 (ASP-HIS-GLY), which is

found in a loop between two helixes

Use phi/psi parameters of these three residues for a search

Asx turn

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3D motif research - continue

The sequences from the hit list:LKY

QGF

DRF

AGV

RGV

DHG

MGK

DNL

HGV

ANN

TGA

QCY

LGA

NSY

Most of these hits were found in loops between helixes

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Pattern search

ZN binding pattern: CXXCXXXFXXXXXLXXHXXXH

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Pattern hits 3D alignment

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Sequence search

• Pseudo multiple sequence alignment (blast output based)• Ligand binding residues are marked• Normalization of hit list to 50% sequence identity

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Helper application for multiple sequences alignment

Blixem as helper browser application for multiple sequences alignment based on blast output

Mime-type: application/x-blast

Blixem http://www.cgb.ki.se/cgb/groups/sonnhammer/Blixem.html

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Helper application for multiple sequences alignment

Jalview as helper browser application for sequences alignment

Mime-type: application/x-align

http://www.jalview.org/

Alignment of Zinc binding PROSITE patter hits

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Sequence hits 3D alignment

2 hits with less than 25% sequence identity

Fragments alignment Chains alignment

EMBL-EBI Secondary structure patterns

Where N binds sugar: Man or Nag

Strand – turn – Strand

Glycosylation pattern N{P}[ST]{P}

2-3 residues gap

EMBL-EBISecondary structure patterns - continue

EMBL-EBISecondary structure patterns - continue

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MSD motif

Small 3D motifs from J.Milner-White search/viewSecondary structure patterns (HTH) search/view,, based search/viewLigands and their environment search/view Catalytic sites search/viewBlast sequence search/viewPROSITE format compliant patterns search/view3D and sequence multiple alignmentHit list and statistics normalization by SCOP,CATH

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MSDmotif as web service

XML query MSDmotif server XML respond as eFamily XML

www.eFamily.org.uk

Hydrogen bonds,, angles

Secondary structures + small motifsSecondary structure patterns

Sequence patternsBlast sequences

Prosite, Catalytic sites, MeropsLigands, fragments, SMILEs

Ligand interactionsArithmetic operations

XML query

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XML query example

Task:Find PDB entries where a ligand is capping a helix and at the same time binds its N-termini.

<?xml version="1.0" encoding="UTF-8" ?>   <!DOCTYPE query …> - <query useUndefinedBonds="yes" phipsiDeviation="10" eValue="auto">- <declaration> <ligand>x l</ligand>   <ss>H h</ss>   </declaration>  <interaction>l.[O]<->h.first.N=H</interaction>   <interaction>l.[O]<->h.last.N<3.5</interaction>   </query>

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Extending eFamily XML

Standard ways of extending an XML schema:- extension- restriction- substitution group

segment

HelixStrandBeta-turnGamma-turnAlpha-beta-motifAsx-turnST-turnST-staple…

entry pdb-entry

entityChainBound-moleculeWater-group

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MSD motif

• www.ebi.ac.uk/msd-srv/msdmotif

• 32000 PDBs, 25 G disk space on Oracle DB, linear dependency~ 0.8 M per PDB

• Web application server with J2EE servlet engine

• NCBI Blast for sequence search

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MSDmotif future development

• 3D alignment extension• Water interactions• Statistical analysis and presentation

– Secondary structure patterns– Statistics from MSDmotif hit list– Correlation of different parameters like

residues weight, csi/phi/psi angles. • Neural network for recognition of complex

structure fragments/motifs in a PDB and their function association