Amino-terminal protein-protein interaction motif (POZ-domain)
Ev olut ion teaches predic ting protein func tionSH3 Src-homology 3 domain one domain of proteins...
Transcript of Ev olut ion teaches predic ting protein func tionSH3 Src-homology 3 domain one domain of proteins...
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Evolution teaches predicting protein function
Burkhard RostCUBIC, NESG, C2B2
Dept. Biochemistry & Mol. Biophysics Columbia University
http://www.rostlab.org/Google “rost”1
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
I. Introduction:protein function
evolution
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Protein function
Intuitive but not well-defined:• chemical how atom bound?• biochemical transferase• cellular (kinase) cell cycle• developmental time, regulatory• physiological related to disease• genetic dominant/recessive
Protein function as action: Function =
anything that happens to or through a protein
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /704
Our goals
Predict protein function from sequence + structure• Where?
nuclear/cytoplasmic/extra-cellular/mitochondrial/other, membrane/not/which, nuclear matrix, ER/Golgi/vesicle?
• What?protein-protein, protein-DNA, protein-small substrate, “is enzyme”, “is cell-cycle control protein”, “SNP deleterious?”
• When?pathways
Predict protein structure: focus on aspects relevant for function
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Sarah Gilman
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Gap sequence/annotation grows!
>7 million protein sequences known by fall 2006>100 million“gene”
sequences
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /707
Less than 25% have some annotation
B Rost, Nair, Liu, Wrzeszczynski & Ofran 2003 CMLS 60 2637-50
coverage of homology transfer
< 10-25%
we clearly need something more!
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /708
Prediction in terms of energy landscapes
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /708
Prediction in terms of energy landscapes
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /708
Prediction in terms of energy landscapes
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /708
Prediction in terms of energy landscapes
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /708
Prediction in terms of energy landscapes
Need to know history to predict!
Point mutationBinding (Substrate/Protein)Environmental change (DNA close/pH)
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Evolution is history!
B Rost 1999 Prot Engin 12:85-94
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1 50fyn_human VTLFVALYDY EARTEDDLSF HKGEKFQILN SSEGDWWEAR SLTTGETGYIyrk_chick VTLFIALYDY EARTEDDLSF QKGEKFHIIN NTEGDWWEAR SLSSGATGYIfgr_human VTLFIALYDY EARTEDDLTF TKGEKFHILN NTEGDWWEAR SLSSGKTGCIyes_chick VTVFVALYDY EARTTDDLSF KKGERFQIIN NTEGDWWEAR SIATGKTGYIsrc_avis2 VTTFVALYDY ESRTETDLSF KKGERLQIVN NTEGDWWLAH SLTTGQTGYIsrc_aviss VTTFVALYDY ESRTETDLSF KKGERLQIVN NTEGDWWLAH SLTTGQTGYIsrc_avisr VTTFVALYDY ESRTETDLSF KKGERLQIVN NTEGDWWLAH SLTTGQTGYIsrc_chick VTTFVALYDY ESRTETDLSF KKGERLQIVN NTEGDWWLAH SLTTGQTGYIstk_hydat VTIFVALYDY EARISEDLSF KKGERLQIIN TADGDWWYAR SLITNSEGYIsrc_rsvpa .......... ESRIETDLSF KKRERLQIVN NTEGTWWLAH SLTTGQTGYIhck_human ..IVVALYDY EAIHHEDLSF QKGDQMVVLE ES.GEWWKAR SLATRKEGYIblk_mouse ..FVVALFDY AAVNDRDLQV LKGEKLQVLR .STGDWWLAR SLVTGREGYVhck_mouse .TIVVALYDY EAIHREDLSF QKGDQMVVLE .EAGEWWKAR SLATKKEGYIlyn_human ..IVVALYPY DGIHPDDLSF KKGEKMKVLE .EHGEWWKAK SLLTKKEGFIlck_human ..LVIALHSY EPSHDGDLGF EKGEQLRILE QS.GEWWKAQ SLTTGQEGFIss81_yeast.....ALYPY DADDDdeISF EQNEILQVSD .IEGRWWKAR R.ANGETGIIabl_mouse ..LFVALYDF VASGDNTLSI TKGEKLRVLG YnnGEWCEAQ ..TKNGQGWVabl1_human..LFVALYDF VASGDNTLSI TKGEKLRVLG YnnGEWCEAQ ..TKNGQGWVsrc1_drome..VVVSLYDY KSRDESDLSF MKGDRMEVID DTESDWWRVV NLTTRQEGLImysd_dicdi.....ALYDF DAESSMELSF KEGDILTVLD QSSGDWWDAE L..KGRRGKVyfj4_yeast....VALYSF AGEESGDLPF RKGDVITILK ksQNDWWTGR V..NGREGIFabl2_human..LFVALYDF VASGDNTLSI TKGEKLRVLG YNQNGEWSEV RSKNG.QGWVtec_human .EIVVAMYDF QAAEGHDLRL ERGQEYLILE KNDVHWWRAR D.KYGNEGYIabl1_caeel..LFVALYDF HGVGEEQLSL RKGDQVRILG YNKNNEWCEA RlrLGEIGWVtxk_human .....ALYDF LPREPCNLAL RRAEEYLILE KYNPHWWKAR D.RLGNEGLIyha2_yeastVRRVRALYDL TTNEPDELSF RKGDVITVLE QVYRDWWKGA L..RGNMGIFabp1_sacex.....AEYDY EAGEDNELTF AENDKIINIE FVDDDWWLGE LETTGQKGLF
SH3Src-homology 3 domainone domain of proteins such asSrc tyrosine kinase (STK)
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7010
1 50fyn_human VTLFVALYDY EARTEDDLSF HKGEKFQILN SSEGDWWEAR SLTTGETGYIyrk_chick VTLFIALYDY EARTEDDLSF QKGEKFHIIN NTEGDWWEAR SLSSGATGYIfgr_human VTLFIALYDY EARTEDDLTF TKGEKFHILN NTEGDWWEAR SLSSGKTGCIyes_chick VTVFVALYDY EARTTDDLSF KKGERFQIIN NTEGDWWEAR SIATGKTGYIsrc_avis2 VTTFVALYDY ESRTETDLSF KKGERLQIVN NTEGDWWLAH SLTTGQTGYIsrc_aviss VTTFVALYDY ESRTETDLSF KKGERLQIVN NTEGDWWLAH SLTTGQTGYIsrc_avisr VTTFVALYDY ESRTETDLSF KKGERLQIVN NTEGDWWLAH SLTTGQTGYIsrc_chick VTTFVALYDY ESRTETDLSF KKGERLQIVN NTEGDWWLAH SLTTGQTGYIstk_hydat VTIFVALYDY EARISEDLSF KKGERLQIIN TADGDWWYAR SLITNSEGYIsrc_rsvpa .......... ESRIETDLSF KKRERLQIVN NTEGTWWLAH SLTTGQTGYIhck_human ..IVVALYDY EAIHHEDLSF QKGDQMVVLE ES.GEWWKAR SLATRKEGYIblk_mouse ..FVVALFDY AAVNDRDLQV LKGEKLQVLR .STGDWWLAR SLVTGREGYVhck_mouse .TIVVALYDY EAIHREDLSF QKGDQMVVLE .EAGEWWKAR SLATKKEGYIlyn_human ..IVVALYPY DGIHPDDLSF KKGEKMKVLE .EHGEWWKAK SLLTKKEGFIlck_human ..LVIALHSY EPSHDGDLGF EKGEQLRILE QS.GEWWKAQ SLTTGQEGFIss81_yeast.....ALYPY DADDDdeISF EQNEILQVSD .IEGRWWKAR R.ANGETGIIabl_mouse ..LFVALYDF VASGDNTLSI TKGEKLRVLG YnnGEWCEAQ ..TKNGQGWVabl1_human..LFVALYDF VASGDNTLSI TKGEKLRVLG YnnGEWCEAQ ..TKNGQGWVsrc1_drome..VVVSLYDY KSRDESDLSF MKGDRMEVID DTESDWWRVV NLTTRQEGLImysd_dicdi.....ALYDF DAESSMELSF KEGDILTVLD QSSGDWWDAE L..KGRRGKVyfj4_yeast....VALYSF AGEESGDLPF RKGDVITILK ksQNDWWTGR V..NGREGIFabl2_human..LFVALYDF VASGDNTLSI TKGEKLRVLG YNQNGEWSEV RSKNG.QGWVtec_human .EIVVAMYDF QAAEGHDLRL ERGQEYLILE KNDVHWWRAR D.KYGNEGYIabl1_caeel..LFVALYDF HGVGEEQLSL RKGDQVRILG YNKNNEWCEA RlrLGEIGWVtxk_human .....ALYDF LPREPCNLAL RRAEEYLILE KYNPHWWKAR D.RLGNEGLIyha2_yeastVRRVRALYDL TTNEPDELSF RKGDVITVLE QVYRDWWKGA L..RGNMGIFabp1_sacex.....AEYDY EAGEDNELTF AENDKIINIE FVDDDWWLGE LETTGQKGLF
SH3Src-homology 3 domainone domain of proteins such asSrc tyrosine kinase (STK)
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7011
Evolution improves prediction
Evolutionary profile implicitly captures history of and individual protein!
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7011
Evolution improves prediction
Evolutionary profile implicitly captures history of and individual protein!
fly
chicken
rat
mouse
human
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7012
Using evolution to predict structure
Sequence PSI-BLAST Filter
PHDsec1993
B Rost 1996 Meth Enzymol 266:525-539
60%->72%/77%
MaxHom
SWIS
S-PROT
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
II. Focus:Predict physical protein-protein interactions
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InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7014
Physical interaction NOT association
PD Kwong, R Wyatt, J Robinson, RW Sweet, J Sodroski & WA Hendrickson (1998) Nature 393, 648-659.PD Kwong, R Wyatt, S Majeed, J Robinson, RW Sweet, J Sodroski & WA Hendrickson (2000) Structure 8, 1329-1339.
gp120
CD4
antibody-1antibody-2
HIV gp120 / CD4 / FAB
YES
YES
NO
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7015
1999: Want to predict protein-protein partners
Simple method failed fully to do this, problem:too many false positives
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7016
Road to predicting protein-protein partners
Implement simple method to do this failed entirely: too many false positives
Reduce false positives:
predict surface residues (PROFacc, 1999) note: 1/2 of residues -> 1/4 of false positives!
predict residues in external interfaces (ISIS, 2004)
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Sarah Gilman
17
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7018
Different interfaces = different physics?
PD Kwong, R Wyatt, J Robinson, RW Sweet, J Sodroski & WA Hendrickson (1998) Nature 393, 648-659.PD Kwong, R Wyatt, S Majeed, J Robinson, RW Sweet, J Sodroski & WA Hendrickson (2000) Structure 8, 1329-1339.
gp120
CD4
antibody-1antibody-2
HIV gp120 / CD4 / FAB
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7019
Find-self test on six types of interfaces
Y Ofran & B Rost 2003 J Mol Biol 325:377-87
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7020
Strength of prediction reflects reliability?
0.6
0.4
0.9
0.1
weakstrong
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7021
PP interfaces predicted from sequence
Very strong =
hot spots?
Y Ofran & B Rost 2003 FEBS Lett 544:236-9Y Ofran & B Rost 2007 Bioinformatics e13-16
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7022
Prediction of hot spots for CD4
• alanine scan for V1 domain of CD4 (bound to gp120)(A Ashkenazi et al. & DJ Capon (1990) PNAS 87, 7150)red: observed
Y Ofran & B Rost 2007 PLoS CB 3, e119
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7022
Prediction of hot spots for CD4
• alanine scan for V1 domain of CD4 (bound to gp120)(A Ashkenazi et al. & DJ Capon (1990) PNAS 87, 7150)red: observed
• structure:PD Kwong et al. & WA Hendrickson (2000) Structure 8, 1329-1339.
purple: predicted(Y Ofran & B Rost (2006) ISIS submitted)
Y Ofran & B Rost 2007 PLoS CB 3, e119
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7023
Hot spots reliably predicted from sequence!
worst:~60%right
hottest of hot = no error!
Y Ofran & B Rost 2007 PLoS CB 3, e119
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7024
Predict protein-protein binding partners
Reducing false positives:predict surface residues (PROFacc, 1999)
predict residues in external interfaces (ISIS, 2004)
predict residues saturated internally (PROFcon, 2004)
localization (e.g. only all nuclear, LOCtree, 2004)
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7025
Predict protein-protein binding partners
Reducing false positives:predict surface residues (PROFacc, 1999)
predict residues in external interfaces (ISIS, 2004)
predict residues saturated internally (PROFcon, 2004)
localization (e.g. only all nuclear, LOCtree, 2004)
predict residues in protein-substrate interfaces (active)
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7026
Predict protein-protein binding partners
Reducing false positives:predict surface residues (PROFacc, 1999)
predict residues in external interfaces (ISIS, 2004)
predict residues saturated internally (PROFcon, 2004)
localization (e.g. only all nuclear, LOCtree, 2004)
predict residues in protein-substrate interfaces (active)
predict protein domains/improve alignments
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7027
Predict protein-protein binding partners
Reducing false positives:predict surface residues (PROFacc, 1999)
predict residues in external interfaces (ISIS, 2004)
predict residues saturated internally (PROFcon, 2004)
localization (e.g. only all nuclear, LOCtree, 2004)
predict residues in protein-substrate interfaces (active)
predict protein domains/improve alignments
Put it all together and predict binding partners
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
III. In passing:Predict subcellular
localization
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InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7029
Predict sub-cellular localization
Homology• sequence similarity
• text similarity
Motifs
De novo• structure
• sequence
KDEL
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Sarah Gilman
30
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7031
Hierarchical prediction system
B Alberts et al. 1994 The Cell Garland R Nair & B Rost 2005 JMB 348:85-100
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7032
Complete map of localization
R Nair & B Rost 2005 JMB 348:85-100
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Sarah Gilman
33
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Protein-protein interactions across compartments
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Extra-cellular
Cytoplasm Organelles Mitochondria
Nuclear TMtransmembrane
Extra-cellular
Cytoplasm
Organelles
Mitochondria
Nuclear
TMtransmembrane
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
PiNat (Protein Interaction Network analysis tool)
35Y Ofran G Yachdav, E Mozes, T Soong, R Nair, B Rost al. 2006 Bioinformatics 15:22 e402-7
Q9P2H0
ADD
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IV. In passing:Model organisms pose problems for protein-protein interactions
36
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Sarah Gilman
37
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
A B
A’ ? B’
similarity > X similarity > X
Can we transfer binding through homology?
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Obviously, otherwise no value in model organisms ...
©Sven Mika & Burkhard Rost (Columbia New York)S Mika & B Rost 2006 PLoS Genetics, Vol 2, e29
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
A B
A’ B’
similarity > X
Inter and Intra-species the same?
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Worm?
A’’
similarity > X
B’’ Human?
©Sven Mika & Burkhard Rost (Columbia New York)
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7040
Much better intra-species
©Sven Mika & Burkhard Rost (Columbia New York)S Mika & B Rost 2006 PLoS Genetics, Vol 2, e29
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Model organisms pose problems for protein-protein interactions
41S Mika & B Rost 2006 PLoS Genetics, Vol 2, e29
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
V. In passing:micro->macro
Connect molecular and systems biology
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InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Sarah Gilman
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InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Connect micro- and macro-level
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micro level:residuesRIGHT: more hotspots
macro level:networks
UP: more partners
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Date- and Party-hubs
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Hubs: promiscuous proteins
Date/Party hubsNotation introduced by Marc VidalJD Han et al. & M Vidal 2004 Nature 430:88-93
• Date hubs interactions at different times/same location?• Party hubs interactions at same time/different location
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
More hotspots -> more party-hub like!
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Non-hubsParty hubsDate hubs
00.10.20.30.40.5
9 26 42
micro: more hotspots
macro: more partners
Y Ofran, A Schlessinger & B Rost submitted
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Natively unstructured regions: induced fit
HJ Dyson & PE Wright 2005 Nat Rev Mol Cell Biol 6:197-208
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
More unstructured -> more date-hub like!
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Non-hubsParty hubsDate hubs
micro: more hotspots
macro: more partners
Y Ofran, A Schlessinger & B Rost 2007 PLoS CB, 3:e140
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
VI. In passing:Structural Genomics
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InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Structural genomics: 1 structure / family for all
50B Rost 1998 Structure 6:259-263
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Speeding up structure determination
• today: more structures in 27 days than in first 27 years
• 8% ‘new sequence-structure family’
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>$15
0M/y
ear
BIG4
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
3D modules
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Multiple 3D alignment identifies consensus secondary structure
© C
hris
tine
Oren
go
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7053
Computational biology & bioinformatics @NESG
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7054
Ta-Tsen Soong
Eyal MozesSara Gilman
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
How many clusters?16,000 MANY MOREProkaryotes only suffices?YES Only for now
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Structural genomics successful?
VERY MUCH AND INCREASINGLY MORE
SO
56
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
SG contributes significantly to novel!
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Every fourth novel protein from 4 US SG centers
J Liu, GT Montelione & B Rost 2007 Nat Biotech 25:849-851
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Structural genomics very effective
58J Liu, GT Montelione & B Rost 2007 Nat Biotech 25:849-851
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Structure provides insight into function
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InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Structure reveals function
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Claudia Bertonati, Sharon Goldsmith-Fischman & Barry Honig, unpublished
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7061
Ta-Tsen Soong
Eyal MozesSara Gilman
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
N’
C’
core/1k8w[251-312]
Common 3D motif/fold
62
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7063
Sequence-based annotation
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Topology
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241 3 5
A
A
core/1k8w[251-312]
241 3 5
A
B
INS2
B
single-I
INS1
241 3 5
A
D
2
multi
INS2
INS1’
624
1 3 5
A
INS3
C
single-II
B
INS2
INS1
most similar?
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
2eve 2ar1 1j2b
Different groups
65
conserved not conservedConSurf F Glaser et al. & N Ben-Tal 2003 Bioinformatics 19:163-4
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
3D reveals: PUA differs from ASCH!
66
241 3 5
A
A
core/1k8w[251-312]
241 3 5
A
B
INS2
B
single-I
INS1
241 3 5
A
D
2
multi
INS2
INS1’
624
1 3 5
A
INS3
C
single-II
B
INS2
INS1
PUAASCHdiffer!
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7067
Other highlights
D Przybylski & B Rost 2007 NAR 35:2238-2246
The FANTOM Consortium 2005 Science 309:1559-1563
A Schlessinger + PLoS CB 2007 3: e140 + Bioinformatics in press + to submit
Y Bromberg& B Rost 2007 NAR 35:3823-3835
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /70
Conclusions
68
Transient protein-protein interfaces specific -> specific prediction very accurate
Localization predicted at levels of accuracy similar to high-throughput experiments
Evolution provides key for de novo prediction of (protein) function
NO key without SWISS-PROT/TrEMBL
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7069
Thanksgiving
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7069
Thanksgiving
Sarah Gilman
InCoB, Hong Kong, Aug 29, 2007 © Burkhard Rost (Columbia New York) /7070
X=http://www.rostlab.orgPredictProtein PP X/predictprotein/
META-PP X/meta/submit_meta.htmlEVA X/eva/services: X/services/
LOCtree X/services/loctree/PredictNLS X/predictNLS/NORSp X/services/norsp/DSSPcont X/services/dsspcont/NLProt X/services/nlprot/CHOP/CHOPnet X/services/chop/ISIS X/services/isis/
databases: X/db/PEP X/db/PEP/CellCycleDB X/db/cellcycledb/NMPdb X/db/nmpdb/