paulino gómez puertas centro de astrobiología master bioinformática. abril 2003. predicción de...
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Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Predicción de estructura de proteínas.
Centro de Astrobiología. CSIC-INTA
Abril 2003
Paulino Gómez-Puertas.
MASTER BIOINFORMÁTICA 2003.
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
by: R. Guigó
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Molecular chaperonin GroEL
subunit
heptamer
(Dr Jianpeng Ma, Harvard Univ.)
ATP
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
From DNA sec. to protein
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
by D. Devos
Genome sequencing.
Tamaños milesORFs MbasesMycoplasma 0.6 Bacterias 3-4 1-4Levadura 6 16Humano 70-125 3200
Growth of EMBL
1994 1995 1996 1997 1998 1999 2000 20011,00E+02
1,00E+03
1,00E+04
1,00E+05
1,00E+06
1,00E+07
H. sapiens
E. coli
S. cerevisiae
C. elegans
D. melanogaster
H. influenzae
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Function
Sequence
Structure
Sequence, structure and function
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Why protein structure prediction?
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
DnaK
FtsA
Actin
Hexokinase
Hsc70
MreB
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Structural alignment
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Protein structure determination
Xray crystallography NMR
By D. Devos
USANortheast Struct. Genomics Research Consor. Rutgers U.NY Struct. Genomics Research Rockefeller U.Southeast Collab. Struct. Genomics U. GeorgiaStruct. Genomics Center Lawrence Berkeley Natl. Lab.Joint Center for Struct. Genomics Scripps Research Inst.Tuberculosis Bact. Struct. Genomics Consort Los Alamos Natl. Lab.Midwest Center for Struct. Genomics Argonne Natl. Lab.
OthersCNRS Orsay/Gif-sur-YvetteProtein Structure Factory BerlinNMR facility OxfordAstex Technology CambridgeRIKEN Tokyo
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
EMBL
PDB
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
MAKEFGIPAA VAGTVLNVVE AGGWVTTIVS ILTAVGSGGL SLLAAAGRES IKAYLKKEIKKKGKRAVIAW
Physical principles: not in the next few years?
Informatics (copying from known cases)
- Homology modeling
Score = 85.1 bits (208), Expect = 6e-19 Identities = 27/56 (48%), Positives = 42/56 (74%), Gaps = 1/56 (1%)
Query: 2 FIAIYDYKAETEEDLTIK KGEKLEIIEKEGD-WWKAKAIGSGEIGYIPANYIAAAE 56 F+A+YDY+A TE+DL+ KGEK +I+ WW+A+++ +GE GYIP+NY+A +Sbjct: 8 FVALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARSLTTGETGYIPSNYVAPVD 63
- Threading
MAKEFGIPAA VAGTVLNVVE AGGWVTTIVS ILTAVGSGGL SLLAAAGRES IKAYLKKEIKKKGKRAVIAW
Pseudo-Energy level?
PDB
Fold ranking
By D. Devos
Protein structure prediction
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
http://folding.stanford.edu/
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
CA(2+)-REGULATED ACTIN-BINDING PROTEIN.
VILLIN CONSISTS OF A LARGE CORE FRAGMENT, THE AMINO-TERMINAL PORTION, AND A SMALL HEADPIECE, THE CARBOXYL-TERMINAL PORTION. THE HEADPIECE BINDS F-ACTIN STRONGLY IN BOTH THE PRESENCE AND ABSENCE OF CALCIUM.
MAJOR COMPONENT OF MICROVILLI OF INTESTINAL EPITHELIAL CELLS.
The folding time is on the order of 10 micro-seconds.
3 Phe
1 Trp
1 Phe
Folding@home: Simulations of the villin headpiece
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Folding@home: Unfolding of HIV integrase (DNAb dom.) HIV uses
proteins to insert its genetic code into our DNA. The DNA binding domain of HIV integrase is the protein which HIV uses to grab onto our DNA such that it can then connect its genetic code into ours. This movie shows a single trajectory of the unfolding of this protein under extreme denaturating conditions.
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
MAKEFGIPAA VAGTVLNVVE AGGWVTTIVS ILTAVGSGGL SLLAAAGRES IKAYLKKEIKKKGKRAVIAW
Physical principles: not in the next few years?
Informatics (copying from known cases)
- Homology modeling
Score = 85.1 bits (208), Expect = 6e-19 Identities = 27/56 (48%), Positives = 42/56 (74%), Gaps = 1/56 (1%)
Query: 2 FIAIYDYKAETEEDLTIK KGEKLEIIEKEGD-WWKAKAIGSGEIGYIPANYIAAAE 56 F+A+YDY+A TE+DL+ KGEK +I+ WW+A+++ +GE GYIP+NY+A +Sbjct: 8 FVALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARSLTTGETGYIPSNYVAPVD 63
- Threading
MAKEFGIPAA VAGTVLNVVE AGGWVTTIVS ILTAVGSGGL SLLAAAGRES IKAYLKKEIKKKGKRAVIAW
Pseudo-Energy level?
PDB
Fold ranking
By D. Devos
Protein structure prediction
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Lesk & Chothia, 1986
Structure & sequence similarity
Sander & Schneider, 1991
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Structure to function
(some examples)
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Hydroxymethylglutaryl-CoA lyase
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Hydroxymethylglutaryl-CoA lyase
S75
D42R41
L263
E279
H233
D204
S201
E279S75
V70
S201
L263D42 R41H233
D204
H233
D204
S75D42
L263
NC
C
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Hydroxymethylglutaryl-CoA lyase
R75
D42
S75
S201
H233D204
Y201
B
A
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Estrogen Receptor-DNA binding. The estrogen receptor recognizes and binds specific sequences of DNA. Upon binding, the protein induces bending in the DNA axis.
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
High Density Lipoprotein Particle. The model surrounded a circular disk of 160 lipids, forming a bilayer, with two apoA-I proteins and 6000 water molecules, altogether a 46,000 atom system.
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Kinesin is a force-generating enzyme, or motor protein, which converts the free energy of the gamma phosphate bond of ATP into mechanical work. This work is used to power the transport of intracellular organelles along microtubules.
Kinesin Motility
http://www.proweb.org/~kinesin/ Liz Greene, Steve Henikoff & Sharyn Endow
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Kinesin itself is an alpha2-beta2 heterotetramer of two heavy and two light chains
How does kinesin walk along a MT protofilament?
http://mc11.mcri.ac.uk/wrongtrousers.html Rob Cross & Minia Alonso
Floppy logic model
Twisting
model
Alternate-sides model
Kinesin Motility
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Neurospora crassa kinesin
Mandelkow lab
Song et al. (2001)
http://www.mpasmb-hamburg.mpg.de/ktdock/
Kinesin Motility
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Kinesin Motility
Model of kinesin dimer walking along a microtubule protofilament. (Hoenger et al.2000).
Mandelkow lab http://www.mpasmb-hamburg.mpg.de/ktdock/
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Kinesin Motility
Ron Milligan Labhttp://www.scripps.edu/milligan/projects.html
Animated Model for Muscle Myosin-Based Motility
Animated Model for Processive Motility by Kinesin
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
Centro de Astrobiología (CSIC-INTA)
Bioinformatics Lab.
Eduardo López ViñasUgo BastollaPaulino Gómez-Puertas
Paulino Gómez PuertasCentro de Astrobiología
Master Bioinformática.Abril 2003.
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