Transcript Project HOPE - WHAT IF servers

HOPE
Have (y)Our Protein Explained
Marlou Snelleman
2011
Overview
 When and why do you use HOPE?
 How to use HOPE?
 How does HOPE work?
When and why do you use HOPE?
 HOPE is useful when you are studying (point)
mutations on protein level
 Using HOPE can save a lot of time
 Pre-select mutations that are expected to have effect
 Quick information without examining multiple databases
and programs
 No need for complete knowledge of bioinformatics
How to use HOPE?
 HOPE needs the sequence as input
How to use HOPE?
How does HOPE work?
PDB
BLAST
Structure
or model
No
structure
Structural
analysis
DASservers
Structural
information
Uniprot
Input
HSSP
Comparison of
properties
Conservation
scores
Additional
Additional
Additional
information
information
information
Output
Output
Input
BLAST
 The sequence
 Object: The sequence
 The mutation
 Tool: BLAST
 Information:
 Uniprot
 Additional information
 Domains, active sites,
phosphorylation sites, contacts,
cysteine bridges, variants etc.
 PDB
 Structural information
Uniprot
 Database that contains
 Protein sequences
 Protein information
 Function
 Origin
 Position of active site(s)
 Position of phosphorylation site(s)
 Domains
 Etc.
 Cross-links to other databases
 Etc.
PDB
Structure or model
 100% identity?
 Use this PDB structure
 Less than 100% identity?
 Make a model
 when the sequences are longer than 80 amino
acids and the identity is higher than 25% (Sander
and Schneider curve)
 with the YASARA and WHAT IF Twinset
Structure or model
Structural analysis
 Object: Structure or model
 Tool: WHAT IF
 Information: Clashes,
disturbed contacts, etc.
PDB
No structure
 Object: The sequence
 Tool: DAS-servers
 Information: prediction of for example
phosphorylation sites.
HSSP
Conservation scores
 Object: The sequence
 Tool: HSSP
 Information: conservation scores
Comparison of properties
 Object: The wild type and the mutant amino acids
 Information: comparison of the different properties of
the amino acids
Output
One example: LRTOMT
 Mutations in the LRTOMT gene cause deafness
 One of these mutations:Y111L
One example: LRTOMT
 HOPE: