markus a function annotation server for protein structures
DESCRIPTION
MarkUs A Function Annotation Server for Protein Structures. Markus Fischer, Donald Petrey, and Barry Honig Columbia University Center for Computational Biology and Bioinformatics NorthEast Structural Genomics Consortium. The importance of exploiting structure-function relationships. 571. - PowerPoint PPT PresentationTRANSCRIPT
MarkUsA Function Annotation Server for Protein Structures
Markus Fischer, Donald Petrey, and Barry Honig
Columbia UniversityCenter for Computational Biology and Bioinformatics
NorthEast Structural Genomics Consortium
The importance of exploiting structure-function relationships
5
304
115
146
1
PSI-BLASTPfamStructure
571
Sequence analysis and
structure analysis
List of neighborsList of target properties
AYWLMKSEPDEFSISDLQ LYWL-KSEPDLFSIT-LVIYFLFKT--DTFSIDTLK
1.
2.
3.
Prediction of function
keywords
Static annotation
pages
Not designed for hypothesis-driven queries
How to identify false positives?
Sequence Analysis
Query: 1 AYWLMKSEPDEFSISDLQ AYWL K+EPD FSI L+Sbjct: 2 AYWLFKTEPDTFSIDTLK
Sequence neighbors
Protein families and motifs
InterPro
Structure Analysis
Structural neighbors
Skan
Electrostatic surface potentials
DelPhi
Residue conservation
ConSurf
Solvent accessible cavities
Screen
Interactive Annotation Map Gene Ontology
UniProt
Ligand contacts
ChEBI Ontology
Integrate Structure
Two example applications for the MarkUs server
1. Testing a hypothesis on protein function
Does NESG target 2eve interact with tRNA?
2. Identification of a binding site
Where does sugar bind to VP8?
General introduction to the MarkUs interface
Display cavities
High Low
Map residue conservation
Negative Positive
Map electrostatic potentials
NESG target PsR62 (PDB 2eve)
ASCH family
PUA domains
YTH domains
connected to RNAmetabolism
known to interactwith tRNA
potential mRNA binding domains
Structural neighbors
Hypothesis: 2eve binds RNA
How to identify RNA binding structural neighbors
How to define a subset of structural neighbors
Identify a structural neighbor of interest
Superimpose a structural neighbor
NESG target2eve
PUA domain1j2b
Residue conservation Electrostatic potentials
High Low Negative Positive
Testing the hypothesis
VP8* carbohydrate-recognizing domain From porcine CRW-8 rotavirus
How to identify a postulated sugar binding site?
Identify sugar binding structural neighbors
Identify sugar binding structural neighbors
Identify sugar binding structural neighbors
Identify sugar binding structural neighbors
Identify sugar binding structural neighbors
Define subset of sugar binding structural neighbors
Define a subset of structural neighbors
Identify sugar binding sites
postulated 2nd binding site
NESG software and databases
SkylineHigh throughput modeling
PudgeRefined models
MarkUshttp://luna.bioc.columbia.edu/honiglab/mark-us/
SkybaseModels database
(NESG, PDB)
MarkUsRepository
(NESG, PDB)
NESG software and databases
SkylineHigh throughput modeling
PudgeRefined models
MarkUshttp://luna.bioc.columbia.edu/honiglab/mark-us/
SkybaseModels database
(NESG, PDB)
MarkUsRepository
(NESG, PDB)
geWorkbench -> genomic data
Conclusions
• System for hypothesis-driven protein function annotation by comparison of local functional features
• Interactive system guided by biological knowledge
• Fast access to function annotations for protein structures
Acknowledgements
National Institutes of Health
Thanks to the
HonigLab
and
for financial support
(grant U54-GM074958)