Dressing up Protein Sequences with Bioinformatics Data

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Dressing up Protein Sequences with
Bioinformatics Data
Cédric Notredame
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Before We Start
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Important Things We will not Talk about here !!!
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Finding Out Simple Things About Your Protein
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Doing Biochemistry in your Computer
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Finding Out Simple things On Expasy
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ExpasyWhere it all starts
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Expasy is a MAJOR service
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Using ProtParam
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Using ProtParam
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Using ProtParam
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Using ProtParam
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Using ProtParam What it does not do for you!
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Comparing Your Sequence With Itself
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Comparing Your Protein With Itself
-Does my protein contain a repeated domain
? -Does my protein contain low complexity
segments?
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The EMBnet Server
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Dotlet Before Starting
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Dotlet Sequence Input
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Dotlet Getting it to work!
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Dotlet Getting it to work!
Disapointing !!!
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Dotlet Getting it to work!
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Dotlet Getting it to work!
Tunning Dotlet The Right Knob at The Right
Moment
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Dotlet Fixing the Zoom Factor!
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1.Set the ZOOMSo that the ENTIRE Protein
Appears
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Dotlet Choosing the right Window
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2Set the Window SizeTo The domain size
-Repeat size 50 Window Size 51
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Dotlet Using The Threshold
Numberof Dots
Log Curve
Score
Threshold 1
Threshold 2
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Dotlet Using The Threshold
T2
Numberof Dots
BLACK
GREY
WHITE
Score
T1
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Dotlet Choosing the right Window
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3Set the Threshold
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Dotlet Analyzing the Dotlet
Low ComplexityRegion
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Dotlet Analyzing your Dotlet
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Introducing our naked sequence
MALRAGLVLG FHTLMTLLSP QEAGATKADH MGSYGPAFYQ
SYGASGQFTH EFDEEQLFSV DLKKSEAVWR LPEFGDFARF
DPQGGLAGIA AIKAHLDILV ERSNRSRAIN VPPRVTVLPK
SRVELGQPNI LICIVDNIFP PVINITWLRN GQTVTEGVAQ
TSFYSQPDHL FRKFHYLPFV PSAEDVYDCQ VEHWGLDAPL
LRHWELQVPI PPPDAMETLV CALGLAIGLV GFLVGTVLII
MGTYVSSVPR
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Introducing our naked sequence
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1-Simple predictions
2-Repeated regions
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Finding Out about the Secondary Structure of
Your Sequence Trans-Membranedomains
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Predicting Secondary Structures
-Does My Protein Contain A trans-membrane domain
?
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protscale sliding Window Methods
Average
Sliding Window
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protscale sliding Window Methods
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protscale sliding Window Methods
FREL_CANAL
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protscale sliding Window Methods
Window Size Tm Domain size
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protscale sliding Window Methods
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Protscale Making the right Interpretation
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Protscale Making the right Interpretation
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Protscale Making the right Interpretation
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Protscale Making the right Interpretation
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tmHMMpred The state of the art
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tmHMMpred The state of the art
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tmHMMpred The state of the art
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1-Simple predictions
2-Repeated regions
3-Secondary Struc
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Predicting Secondary Structures
-Does My Protein Contain A Coiled-coil domain ?
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Using the EMBnet COILS server
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Using the EMBnet COILS server
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Finding Out about the Secondary Structure of
Your Sequence Helices and Beta-sheet
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Predicting Secondary Structures
-What is the secondary structure of my protein ?
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Running PsiPred
Your email
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Running PsiPred
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How Trustable Is PsiPred ?
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How Trustable Is PsiPred on my protein ?
Do you need to see the homologs?
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Finding Out if your Sequence Is Modified
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Post Translation Modifications
-Is my protein modified after its
translation -Phosphorilated -Glycolated -
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What is a Prosite pattern ?
-A PROSITE Pattern is a Protein WORD conserved in
many sequences
PVAILL
-PROSITE Patterns lets you identify protein
families or important features of your sequence
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What is a Prosite pattern ?
-A PROSITE Pattern Lets You identify a protein
family JUST LIKE the silver lady lets you
identify a certain brand of cars
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Prosite Patterns can describe complex signatures
RK-x-ST
-Reads as Followsan Arginine or a Lysine,
followed by one random residue, followed by a
Serine or a Threonine
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Prosite Patterns can describe complex signatures
C-DES-x-C-x(3)-I-x(3)-R-x(4)-P-x(4)-C-x(2)-C
Is a signature for Zn finger proteins that Bind
DNA
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Using PrositeScan
MALRAGLVLG FHTLMTLLSP QEAGATKADH MGSYGPAFYQ
SYGASGQFTH EFDEEQLFSV DLKKSEAVWR LPEFGDFARF
DPQGGLAGIA AIKAHLDILV ERSNRSRAIN VPPRVTVLPK
SRVELGQPNI LICIVDNIFP PVINITWLRN GQTVTEGVAQ
TSFYSQPDHL FRKFHYLPFV
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Using PrositeScan Short Patterns
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Using PrositeScan Short Patterns
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Using PrositeScan Short Patterns
We cannot do much with this weak but
exciting We can only REMEMBER and WAIT
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Using PROSITE-Scan Structure
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Other Means of Prediction Post Translational
Modifications
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1-Simple predictions
2-Repeated regions
3-Secondary Struc
4-PROSITE motifs
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Identifying Domain
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The Idea of Domains
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The Three Major Resources For Searching Domain
Collections
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Interpro A Federation of Databases
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The Three Major Resources For Searching Domain
Collections
Domain servers ( and domain collections) are like
good Italian restaurant they all look similar,
but each of them is a bit special and has its own
recipes
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Finding Domains
-Is my Protein made of known domains ?
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Interpro The Idea of Domains
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Using InterPro Asking a question
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Using InterPro Asking a question
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Using CDsearch Asking a question
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Using CDsearch Asking a question
NCBI Domain
E-Values
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Finding Domains
-How can I be sure that the domain Prediction of
my Protein is real ?
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Using EMBNet PFscan
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Using EMBNet PFscan
Important Position that is Well conserved in our
sequence
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1-Simple predictions
2-Repeated regions
4-PROSITE motifs
3-Secondary Struc
5-Conserved Domains
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Finding Homologues
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BLAST A summary
-BLAST compares YOUR SEQUENCE with ALL THE
SEQUENCES in a database -BLAST reports the
sequences that are the more similar to your
sequence -If your sequence is more than 30
identical to another sequence (over more than 100
residues) these two sequences probably have the
same origin, the same structure and related
biochemical functions.
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Making Sense of it all with the 3D structure
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Using Structural Information
-What is the 3D structure of my protein ?
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Using Structural InformationBlasting against
PDB
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Finding Structural Homologues with BLAST
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Displaying Your Structure
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Displaying Your Structure
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Displaying Your Structure
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Displaying Your Structure
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Highlighting Interesting Bits
Concistency!!!
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1-Simple predictions
2-Repeated regions
4-PROSITE motifs
5-Conserved Domains
3-Secondary Struc
6-3D structures
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Finding out about the Genetic Environment of your
Protein
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Using Genomic Information
-Where is my protein in the human genome.-Where
are its homologues ?
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Using Genomic Information
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Blasting the Human Genome
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Blasting the Human Genome
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Blasting the Human Genome Finding Out about
the Neighborhood Of your Gene
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Blasting the Human Genome Finding Out about
the Neighborhood Of your Gene
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Blasting the Human Genome Finding Out about
the Neighborhood Of your Gene
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Blasting the Human Genome Finding Out about
the Neighborhood Of your Gene
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Blasting the Human Genome Finding Out about
the Neighborhood Of your Gene
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Wrapping it up!
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1-Simple predictions
2-Repeated regions
4-PROSITE motifs
5-Conserved Domains
3-Secondary Struc
6-3D structures
7-Genomic Environment
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5-Conserved Domains
Two Domains
6-3D structures
Tm Domain
2-Repeated regions
3-Secondary Struc
ImmunologyRelated
5-Conserved Domains
7-Genomic Environment
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