embl-ebi msd motif pdb: 1gci structure annotation and function assignment with msdmotif
TRANSCRIPT
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EMBL-EBI MSD motifwww.ebi.ac.uk/msd-srv/msdmotif
PDB: 1gci
Structure Annotation
and
Function Assignment with MSDmotif
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EMBL-EBI
MSDmotif front options
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EMBL-EBI
Small motifs
Alpha-Beta Motif Nest ST staple
11 motifs in total
Prof James Milner-White
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EMBL-EBI
Small motif stats
Occurrence of amino-acids Correlation of side chain charge
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EMBL-EBI
Small motif stats
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EMBL-EBI
Small motifs – hit list from stats
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EMBL-EBI
Small motifs – 3D alignment
ST-staple
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EMBL-EBI
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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EMBL-EBI
, search
Ideal for short loops search
PDB:1gci
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EMBL-EBI
, search - continue
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EMBL-EBI
, search - continue
PDB:1gciSubtilases family
PDB:1f5pGlobins family
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EMBL-EBI
, 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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EMBL-EBI
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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EMBL-EBI
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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EMBL-EBI
Pattern search
ZN binding pattern: CXXCXXXFXXXXXLXXHXXXH
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EMBL-EBI
Pattern hits 3D alignment
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EMBL-EBI
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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EMBL-EBI
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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EMBL-EBI
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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EMBL-EBI
Sequence hits 3D alignment
2 hits with less than 25% sequence identity
Fragments alignment Chains alignment
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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
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EMBL-EBISecondary structure patterns - continue
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EMBL-EBISecondary structure patterns - continue
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EMBL-EBI
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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EMBL-EBI
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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EMBL-EBI
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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EMBL-EBI
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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EMBL-EBI
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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EMBL-EBI
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