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Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril 2003. Predicción de estructura de proteínas. Centro de Astrobiología. CSIC-INTA.

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Presentation on theme: "Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril 2003. Predicción de estructura de proteínas. Centro de Astrobiología. CSIC-INTA."— Presentation transcript:

1 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Predicción de estructura de proteínas. Centro de Astrobiología. CSIC-INTA Abril 2003 Paulino Gómez-Puertas. MASTER BIOINFORMÁTICA 2003.

2 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril by: R. Guigó

3 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Molecular chaperonin GroEL subunit heptamer (Dr Jianpeng Ma, Harvard Univ.) ATP

4 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril From DNA sec. to protein

5 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril by D. Devos Genome sequencing. TamañosmilesORFs Mbases Mycoplasma0.6 Bacterias Levadura 616 Humano Growth of EMBL H. sapiens E. coli S. cerevisiae C. elegans D. melanogaster H. influenzae

6 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Function Sequence Structure Sequence, structure and function

7 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Why protein structure prediction?

8 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril 2003.

9 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril DnaK FtsA Actin Hexokinase Hsc70 MreB

10 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Structural alignment

11 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Protein structure determination Xray crystallography NMR By D. Devos USA Northeast Struct. Genomics Research Consor. Rutgers U. NY Struct. Genomics Research Rockefeller U. Southeast Collab. Struct. Genomics U. Georgia Struct. 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. Others CNRS Orsay/Gif-sur-Yvette Protein Structure Factory Berlin NMR facility Oxford Astex Technology Cambridge RIKEN Tokyo

12 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril EMBL PDB

13 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril MAKEFGIPAA VAGTVLNVVE AGGWVTTIVS ILTAVGSGGL SLLAAAGRES IKAYLKKEIK KKGKRAVIAW 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 AGGWVTTIV S ILTAVGSGGL SLLAAAGRES IKAYLKKEIK KKGKRAVIAW Pseudo-Energy level? PDB Fold ranking By D. Devos Protein structure prediction

14 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril

15 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril 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 Simulations of the villin headpiece

16 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril 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.

17 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril MAKEFGIPAA VAGTVLNVVE AGGWVTTIVS ILTAVGSGGL SLLAAAGRES IKAYLKKEIK KKGKRAVIAW 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 AGGWVTTIV S ILTAVGSGGL SLLAAAGRES IKAYLKKEIK KKGKRAVIAW Pseudo-Energy level? PDB Fold ranking By D. Devos Protein structure prediction

18 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Lesk & Chothia, 1986 Structure & sequence similarity Sander & Schneider, 1991

19 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril 2003.

20 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Structure to function (some examples)

21 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Hydroxymethylglutaryl-CoA lyase

22 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Hydroxymethylglutaryl-CoA lyase S75 D42 R41 L263 E279 H233 D204 S201 E279 S75 V70 S201 L263 D42 R41 H233 D204 H233 D204 S75 D42 L263 N C C

23 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Hydroxymethylglutaryl-CoA lyase R75 D42 S75 S201 H233 D204 Y201 B A

24 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Estrogen Receptor-DNA binding. The estrogen receptor recognizes and binds specific sequences of DNA. Upon binding, the protein induces bending in the DNA axis.

25 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril 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.

26 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril 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 Liz Greene, Steve Henikoff & Sharyn Endow

27 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Kinesin itself is an alpha2-beta2 heterotetramer of two heavy and two light chains How does kinesin walk along a MT protofilament? Rob Cross & Minia Alonso Floppy logic model Twisting model Alternate-sides model Kinesin Motility

28 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Neurospora crassa kinesin Mandelkow lab Song et al. (2001) Kinesin Motility

29 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Kinesin Motility Model of kinesin dimer walking along a microtubule protofilament. (Hoenger et al.2000). Mandelkow lab

30 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Kinesin Motility Ron Milligan Lab Animated Model for Muscle Myosin-Based Motility Animated Model for Processive Motility by Kinesin

31 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril Centro de Astrobiología (CSIC-INTA) Bioinformatics Lab. Eduardo López Viñas Ugo Bastolla Paulino Gómez-Puertas

32 Paulino Gómez Puertas Centro de Astrobiología Master Bioinformática. Abril End of slide show


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