Transcript MSD motif - European Bioinformatics Institute

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MSD motif
www.ebi.ac.uk/msd-srv/msdmotif
Structure Annotation
and
Function Assignment with
MSDmotif
PDB: 1gci
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MSDmotif front options
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Small motifs
Alpha-Beta Motif
Nest
11 motifs in total
Prof James Milner-White
ST staple
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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
Ligands
Catalytic sites
ProSite
Small motifs
“Group” menu
item contains a
list of presented
in a PDB entry
sites and motifs
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, search
PDB:1gci
Ideal for short loops
search
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, search - continue
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, search - continue
PDB:1gci
Subtilases family
PDB:1f5p
Globins family
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, search vs sequence search
Sequences found while search
by , :
Subtilases family
NNSIGVL
DNTTGVL
DNSIGVL
Globins family
IVDTGSV
Blast search for
NNSIGVL
Diphtheria toxin family
SDSIGVL
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3D motif research
Asx turn
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
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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
Alignment
of Zinc
binding
PROSITE
patter hits
Jalview as helper browser
application for sequences
alignment
Mime-type:
application/x-align
http://www.jalview.org/
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Sequence hits 3D alignment
2 hits with less than 25% sequence identity
Fragments alignment
Chains alignment
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Secondary structure patterns
Strand – turn – Strand
2-3 residues gap
Glycosylation pattern N{P}[ST]{P}
Where N binds sugar: Man or Nag
Secondary structure patterns continue
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Secondary structure patterns continue
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MSD motif
Small 3D motifs from J.Milner-White search/view
Secondary structure patterns (HTH) search/view
,, based search/view
Ligands and their environment search/view
Catalytic sites search/view
Blast sequence search/view
PROSITE format compliant patterns search/view
3D and sequence multiple alignment
Hit 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 motifs
Secondary structure patterns
Sequence patterns
Blast sequences
Prosite, Catalytic sites, Merops
Ligands, fragments, SMILEs
Ligand interactions
Arithmetic 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
entry
pdb-entry
segment
entity
Chain
Bound-molecule
Water-group
Helix
Strand
Beta-turn
Gamma-turn
Alpha-beta-motif
Asx-turn
ST-turn
ST-staple
…
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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