Title: Integraci
1Integración de datos evolutivosen la predicción
de estructura y función
Alfonso Valencia CNB - CSIC
2ran
rcc1
by J.A. G-Ranea
3Cluster of solutions 2
Cluster of solutions 1
Solution 3
Solution 4
by J.A. G-Ranea
4ran
rcc1
by J.A. G-Ranea
5Mapping of tree determinants
Model
6Azuma et al., J,Mol. Biol. 1999
7Mapping of mutants (side view)
Model
H270
GDP
D44
Mg
H304
E157
H410
R206
H78
D128
Green Km, red Kcat.
8Model and Xray
Ran
Ran
SO4
Mg
GDP
Rcc1
Rcc1
Model
Complex
9Ran (SO4) Rcc1
Ran (GDP-Mg) Rcc1
Complex
Complex/Docking superposition
Model
GRAMM results
Model/Docking superposition
10Mapping of mutants (side view)
Complex (Model on Vomplex superposition)
Model
GDP
H270
Mg
GDP
D44
Mg
H304
H304
D44
H410
E157
E157
H78
H78
H410
R206
H78
R206
H78
H270
D128
D128
Green Km, red Kcat.
11Mapping of tree determinants
Model
Complex
12Functional specificity in the ras superfamily
Ral
Rlip (coiled-coil)
Ras Binding Domain folding
Ras
By J.A. Ranea
13The space of sequences
Treedeterminants
Sequencespace (Casari, Sander, Valencia, Nature.
Str. Bio. 95)
Ras
Ral
Rho
Ras
36 and 37 main tree-determinant positions
Ral
Rho
Yeast Two-Hybrid Experiments (Bauer et. al. JBC
1999)
by J.A. G-Ranea
14DnaK
Actin
Hsc70
MreB
Hexokinase
FtsA
15(No Transcript)
16A dimerization model for FtsA
Löwe et al., Nature 00
Carettoni, et al., (2002) Phage-display and
correlated mutations identify an essential region
of subdomain 1C involved in homodimerization of
Escherichia coli FtsA Proteins
17Information extracted from multiple sequence
alignments
Ras
Ral
Rho
18Prediction of interaction regions
Multiple sequence alignment
5 6 10 20 22 30
A V . . W Y
Sequence profiles
Interface No
aa.
5,6,10,20,22,30
3D str. Surface patch
Fariselli, et al., (2002). Prediction of
protein-protein interaction sites with neural
networks. Eur J Biochem
19Prediction of protein interaction sites with
neural networks
Goal Predict surface residue in contact with
another protein. Method Feed-forward neural
network trained with standard back-propagation. O
utput layer Single neuron representing contact /
no contact Hidden layer 4 nodes Input layer -
Patches in protein structures (sets of exposed
neighbour residues) 11 residue-long window,
central surface residue 10 patch neighbours -
Evolutionary information Residue coded as a
vector corresponding to frequencies in the
MSA Result 73 average accuracy of correctly
predicted interacting residues
Fariselli, Pazos,Valencia, Casadio, Eur. J.
Biochem. 02
20Results of the predictions of protein interaction
sites
Fariselli, Pazos,Valencia, Casadio, Eur. J.
Biochem. 02
21NN predictions of interaction regions
Carettoni, et al., (2002) Phage-display and
correlated mutations identify an essential region
of subdomain 1C involved in homodimerization of
Escherichia coli FtsA Proteins
22(No Transcript)
23DnaK
Actin
Hsc70
MreB
Hexokinase
FtsA
24Prediction of interaction regions
Multiple sequence alignment
5 6 10 20 22 30
A V . . W Y
Sequence profiles
Interface No
aa.
5,6,10,20,22,30
3D str. Surface patch
Fariselli, et al., (2002). Prediction of
protein-protein interaction sites with neural
networks. Eur J Biochem
25Prediction of protein interaction sites with
neural networks
Goal Predict surface residue in contact with
another protein. Method Feed-forward neural
network trained with standard back-propagation. O
utput layer Single neuron representing contact /
no contact Hidden layer 4 nodes Input layer -
Patches in protein structures (sets of exposed
neighbour residues) 11 residue-long window,
central surface residue 10 patch neighbours -
Evolutionary information Residue coded as a
vector corresponding to frequencies in the
MSA Result 73 average accuracy of correctly
predicted interacting residues
Fariselli, Pazos,Valencia, Casadio, Eur. J.
Biochem. 02
26Results of the predictions of protein interaction
sites
Fariselli, Pazos,Valencia, Casadio, Eur. J.
Biochem. 02
27A dimerization model for FtsA
Löwe et al., Nature 00
Carettoni, et al., (2002) Phage-display and
correlated mutations identify an essential region
of subdomain 1C involved in homodimerization of
Escherichia coli FtsA Proteins
28NN predictions of interaction regions
Carettoni, et al., (2002) Phage-display and
correlated mutations identify an essential region
of subdomain 1C involved in homodimerization of
Escherichia coli FtsA Proteins
29Carnitine Acyl transferases
2dubE/CPTI/COT/CACP
Carnitine Octanoyltransferase
Carnitine Palmitoyltransferase I
P. Gomez-Puertas / F. G. Hegardt lab
Morillas et al. 2001. J.Biol.Chem. 276, 45001-8,
2001 in the press, and 2002 in the press
30Protein Design Group CNB-CSIC
www.pdg.cnb.uam.es
Miguel A. Peñalva CIB-CSIC
Fausto Edgarth U. Barcelona
Søren Brunak DTU, Copenhagen
Juan Carlos Sanchez TFs in Aspergilus
SH3 B. Distel, Amsterdam
Manuela Helmer-Citterich U. TorVergata,
SANITAS Miguel Vicente CNB - CSIC
Amalia Muñoz binding specificity system
Paulino Gómez Puertas Bacterial Cell Division
Protein Structure Prediction
Rita Casadio Pierro Fariselli U. Bologna
David de Juan Protein interactions
Osvaldo Graña Threading / servers
Manuel Gómez Bacterial Cell division II
EC V FP
Ramón Roca Homology modeling
RAS E. Laue, Cambridge F. Wittinghoer, MPI
Javier Guijarro Interaction networks
Michael Tress Threading
Burkhard Rost Columbia U., NY
Juan Antonio G. Ranea ras signalling system
Luis Sánchez-Pulido Sequence analysis
REGIA J. Pazares, CNB-CSIC
Damien Devos Function prediction at genomic scale
Genome analysis
José María Fernandéz Database design
Christos Ouzounis EBI-EMBL, Cambridge
Ramón Alonso Arabidopsis T. factors
Protein Design
Systems
Julio Collado-Vides UNAM, Cuernavaca.
Armando Amat System management
TEMBLOR EBI EC VFP
Federico Abascal Function prediction
Information Extraction
Antoine de Daruvar Lion, Heidelberg.
CICYT biotech
Florencio Pazos Interaction networks
Roderic Guigo IMIM, Barna
Christian Blaschke Information extraction
Centro de Astrobiología
DNA arrays
Joaquin Dopazo Javier Herrero CNIO
María González Genomics, Ecology
CICYT FEDER
Juan Carlos Oliveros Array data management
ORIEL EMB0 EC VFP
Eduardo Leon Detection of protein names
Ugo Bastolla Protein stability
Keith Harshman, Carlos Martínez D I O - C N B
ALMA Bioinformática S.L.
Andrés Moya, Roeland van Ham U. Valencia
Robert Hoffmann I.E. Biomedicine
Javier Tamames Genome analysis
Prof. Hans Robert Kalbitzer U. Regensburg
Enrique Merino Centro Bioitecnología UNAM,
Cuernavaca
Bioinformatics support Information extraction
Visitors
31Text mining
Biological examples
Protein interactions