Transcript PPT - FLI - Leibniz Institute for Age Research

The Jena Library of Biological Macromolecules – JenaLib
(www.fli-leibniz.de/IMAGE.html)
Jürgen Sühnel
[email protected]
Biocomputing Group
Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena Centre for Bioinformatics
Jena / Germany
(November 2006)
Related information:
Lecture Series ‚3D Structures of Biological Macromolecules‘
http://www.fli-leibniz.de/www_bioc/3D/
Fritz Lipmann
The Journal of Biological Chemistry
186, 235, 1950
Coenzyme A
Computational
Structural Biology
Biocomputing Group: Research and Service
Identification and Analysis of Unusual Structural Motifs in Proteins and
Nucleic Acids
• Water-Mediated Base Pairs
• Base Polyad Motifs in DNA Mutiplex Structures
• C-H...O/N Interactions in RNA Structures
• C-H... Interactions in Proteins (IMB, X-Ray Crystallography: Weiss)
• Nest Motifs and Non-repetitive Dipeptide Patterns in Proteins
Other
Computational
Genomics
(UCLA: Pal; EMBL Hamburg Outstation: Weiss)
Database ‚Jena Library of Biological Macromolecules (JenaLib)‘
Computational Genomics of Prokaryotes
(IMB/FLI Genome Analysis Group: Platzer)
Short-term Collaborative Projects
• Structure and Conformational Analysis of Ampullosporin A
(HKI: Gräfe;
Friedrich Schiller University: Görls, Reissmann)
• Computer Selection of DNA Oligonucleotide Probe Combinations for COMBO-FISH
• Chromatin Structure
(Heidelberg/Freiburg University: Hausmann)
(FLI, Molecular Biology Group: Diekmann)
Websites for Molecular Biology
Service
• The RNA World Website
• The JCB Protein-Protein Interaction Website
Maintenance of the Institutional Computer Network
www.fli-leibniz.de/www_bioc/
Biocomputing Group: Databases, Websites/Webtools
The Jena Library of Biological Macromolecules (JenaLib)
www.fli-leibniz.de/IMAGE.html
The RNA World Website
www.fli-leibniz.de/RNA.html
The JCB Protein-Protein Interaction Website
www.fli-leibniz.de/jcb/
The Jena Prokaryotic Genome Viewer
jpgv.fli-leibniz.de
The Spirochetes Genome Browser
sgb.fli-leibniz.de
Biocomputing Group: Methods
 Quantum Chemistry
 Molecular Dynamics
 (Structural) Bioinformatics
 Computational Genomics
 Database / Website Development
DNA Structure: History
DNA Structure:
History
DNA Structure: Ideal B-DNA Conformation
First Single-Crystal DNA Structure (B-DNA)
Drew-Dickerson structure
H. R. Drew, R. M. Wing, T. Takano, C. Broka, S. Tanaka, K. Itakura, R. E. Dickerson
Structure Of A B-/DNA Dodecamer. Conformation And Dynamics
Proc. Nat. Acad. Sci. Usa V. 78 2179 1981
Protein Structure: The Protein -Helix
The first and still one of the greatest
triumphs of speculative model
building in structural
chemistry/biology
Forerunner of computer-assisted
model building
In the PNAS paper
the helix is drawn left-handed !!!!!
Linus Pauling and Robert Corey with a
wooden model of a protein -helix
(1 inch per Å)
Pauling, Corey, Branson.
The structure of proteins: Two hydrogen-bonded helical conformations of the polypeptide chain.
Proc. Natl. Acad. USA 1951, 37, 205-211.
Protein Structure: Hemoglobin Model
www2.mrc-lmb.cam.ac.uk/archive/Perutz62.html
The Oldest Myoglobin and Hemoglobin Structures in the PDB
Myoglobin (1mbn)
Hemoglobin (2dhb)
2 alpha chains: 146 aa (green, cyan)
2 beta chains: 141 aa (red, brown)
(Watson, Kendrew: 1973)
(Perutz et al.: 1973)
Myoglobin Model Built by A. A. Barker, Model Maker in Cambridge (UK)
www.umass.edu/molvis/francoeur/barker/barker.html
Protein Structure: History
Nobel Prizes for Both DNA and Protein Structures
Structural Biology Nobel Prices
Protein Structure: Thermodynamic Hypothesis
Christian B. Anfinsen
The native structure of a protein
corresponds to the
minimum of free energy.
Protein Structure: Amino Acids
Protein Structure: Amino Acids
www.fli-leibniz.de/IMAGE_AA.html
Internal Co-ordinates
(Bond) Distance
(Bond) Angle
Torsion angle
[2 atoms]
[3 atoms]
[4 atoms]
C
D
B
A
Protein Structure
Sequence
Protein-protein or
protein-nucleic acid
complexes
Secondary structure
elements
Domains/Folds/Chains
Protein Structure: Secondary Structure Elements
Protein Structure: The Protein -Helix
The first and still one of the greatest
triumphs of speculative model
building in structural
chemistry/biology
Forerunner of computer-assisted
model building
In the PNAS paper
the helix is drawn left-handed !!!!!
Linus Pauling and Robert Corey with a
wooden model of a protein -helix
(1 inch per Å)
Pauling, Corey, Branson.
The structure of proteins: Two hydrogen-bonded helical conformations of the polypeptide chain.
Proc. Natl. Acad. USA 1951, 37, 205-211.
Protein Structure: Domains
Structure-based definition
Dali Fold Classification
Sequence-based definition
Protein Domains: JenaLib Jmol Viewer
calcium-free human calpain
Calpains (calcium-dependent cytoplasmic cysteine proteinases) are implicated in processes
such as cytoskeleton remodeling and signal transduction.
Protein Domains: JenaLib Jmol Viewer
Protein Structure: Backbone Torsion Angles
D. W. Mount: Bioinformatics, Cold Spring Harbor Laboratory Press, 2001.
Protein Structure: The Ramachandran Map
Theoretical
Beta-sheet
Left-handed
alpha-helix
Right-handed
alpha-helix
Ramachandran, Ramakrishnan, Sasisekharan.
Stereochemistry and polypeptide chain configurations.
J. Mol. Biol. 1963, 7, 95-99.
Ramachandran, Sasisekheran.
Conformation of polypeptides and proteins.
Adv. Protein. Chem. 1968, 23, 283-438.
Experimental
237 384 amino acids in 1041 protein chains
Hovmöller et al., Acta Cryst. D 2002, 58, 768-776
non-glycines
glycines
PDB Growth Rate
2005: ~ 15 new structures per day
Motivation
There is an insufficient impact of the available 3D structural information
on biopolymers outside structural biology.
1993  IMB Jena Image Library of Biological Macromolecules

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
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Visualization and other analysis tools for complete structures and structure parts
Classification
Extensive cross-referencing
As much information as possible in one place
Related attempt at that time  Swiss-3D-Image
Editorial, Nature Struct. Biol. 1997, 4, 329-330.
Structure and the genome
1992:
2004:
 “rift between the sequence and the structure world”
1006
29841
PDB entries
PDB entries
 “clash of scientific cultures and the inherent complexity of structure
data”
 “even experienced sequence analysts can sort of get ill when they look
at a coordinate file”
 “What do molecular biologists fear most? Three letters: PDB.”
Mission and Features
The IMB Jena Image Library of Biological Macromolecules is aimed at a better dissemination of information on
three-dimensional biopolymer structures with an emphasis on visualization and analysis.
It provides access to all structure entries deposited at the Protein Data Bank (PDB) or at the Nucleic Acid
Database (NDB). In addition, basic information on the architecture of biopolymer structures is available.
The IMB Jena Image Library intends to fulfill both scientific and educational needs.
Basic information on the architecture of biopolymers
Atlas pages for all entries with as much information as possible in one place
Various visualization tools for complete structures and structure parts including a
user-friendly SCOP domain viewer and both raster and vector graphics output
Hetero components database
Site database
Environment analysis of hetero components and sites
Species classification including a PDB structures species timeline
Gene Ontology classification of PDB structures
Comprehensive bending classification of nucleic acid double helix structures
Versatile search options allowing the direct search for identifiers/names from
PDB, NDB, UniProt, Pfam, SMART, SCOP, GO
Links to more than 30 external databases
………….
Cross references from other databases
RNABase
Systers
~ 1 information request per minute
Reichert, Sühnel.
The IMB Jena Image Library of Biological Macromolecules - 2002 update.
Nucleic Acids Res. 2002, 30, 253-254.
Bioinformatics Group
(K. Schmid)
Different Protein Views
Structural Biology
Genomics
Porin
(1a0s)
Cell Biology
Systems Biology
SIR2p – NAD+-dependent histone deacetylase
PNC1 – pyrazinamidase/nicotinamidase
Gallery
Start Page
Start Page
Atlas Page
Atlas Page
UniProt/PDB Alignment Viewer
Bioinformatics Group
(K. Schmid)
UniProt/PDB Alignment Viewer
Bioinformatics Group
(K. Schmid)
UniProt/PDB Alignment Viewer
Bioinformatics Group
(K. Schmid)
Integrated Viewing
Bioinformatics Group
(K. Schmid)
JenaLib
Jmol Viewer
(jmol.sourceforge.net)
Chain A of the structure of the human alcohol beta 1 dehydrogenase (Protein
Data Bank code: 1DEH) is shown in the viewer. The structure consists of the
N-terminal (red) and
C-terminal (blue) alcohol dehydro-genase SCOP
domains. In addition, the following structural features are shown:
- ligands (4-iodopyrazole, NAD;
spacefilling representation),
- Zn-containing active sites,
- PROSITE motif
(thick trace, tomato-colored),
- SAPs from UniProtKB
(wt – magenta, mutated – cyan).
VAR_000426 is assumed to be associated with a lower risk of alcoholism.
Note, that both the SAPs and the PROSITE motif occur in the (red) N-terminal
SCOP domain.
Bioinformatics Group
(K. Schmid)
A Structural Understanding of Friedreich‘s Ataxia
Frataxin
SNP/SAP mutations in frataxin are associated
with Friedreich´s ataxia (FRDA), a recessive
neurodegenerative disorder that involves
progressive loss of voluntary muscular
coordination and heart enlargement and can
lead to death. It is assumed that the condition
arises from disregulation of mitochondrial iron
homeostasis with concomitant oxidative
damage leading to neuronal death
(OMIM : 229300).
Ile 154 Arg is the most common mutation and
leads to a severe phenotype in several
independent families.
Trp 165 Arg involves an absolutely conserved Trp.
G. Musco et. al., Structure 8 (2000), 695
A Structural Understanding of Friedreich‘s Ataxia
JenaLib Jmol Viewer
Frataxin
TRP155->ARG
ILE154->PHE
is exposed and replaces an aromatic by a positively charged sidechain.
is buried but located at the interface between different secondary structure elements.
Here a smaller sidechain is replaced by a larger one.
A Structural Understanding of Friedreich‘s Ataxia
JenaLib Jmol Viewer
Frataxin
TRP155->ARG [W155R]
ILE154->PHE [I154F]
TRP155->ARG
ILE154->PHE
is exposed and replaces an aromatic by a positively charged sidechain.
is buried but located at the interface between different secondary structure elements.
Here a smaller sidechain is replaced by a larger one.
A Structural Understanding of Friedreich‘s Ataxia
Frataxin
Jena Image Library Jmol Viewer
Both SAPs are located in the frataxin family signature site and can probably disturb ligand binding.
Asymmetric vs. Biological Units
Tomato Bushy Stunt Virus (PDB ID: 2TBV)
Asymmetric Unit
Biological Unit
Coloring by:
Asymmetric Unit
Chain
Chain
(a different color is assigned to each unit)
(a different color is assigned to each chain)
(asymmetric unit chain colors)
The complete database information is available
both for asymmetric and biological units.
QickSearch
Bioinformatics Group
(K. Schmid)
Customization of Entry Lists
Bioinformatics Group
(K. Schmid)
Customization of Entry Lists
Bioinformatics Group
(K. Schmid)
Customization of Entry Lists
Bioinformatics Group
(K. Schmid)
PROSITE
Syntax
Hetero Components Database
Cover Images for 2003, 2004, 2005, 2006, 2007, … Issues
of the Journal RNA
Bioinformatics Group
(K. Schmid)