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The Protein Data Bank (PDB)
• PDB is the principal repository for protein structures
• Established in 1971
• Accessed at http://www.rcsb.org/pdb or simply
http://www.pdb.org
• Currently contains over 32,000 structure entities
Updated 9/05
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structures
PDB content growth (www.pdb.org)
year
Fig. 9.6
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PDB holdings (September, 2005)
29,876
1,338
1,500
13
32,727
proteins, peptides
protein/nucl. complexes
nucleic acids
carbohydrates
total
Table 9-2
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gateways to access PDB files
Swiss-Prot, NCBI, EMBL
Protein Data Bank
CATH, Dali, SCOP, FSSP
databases that interpret PDB files
Fig. 9.10
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Access to PDB through NCBI
You can access PDB data at the NCBI several ways.
• Go to the Structure site, from the NCBI homepage
• Use Entrez
• Perform a BLAST search, restricting the output
to the PDB database
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Access to PDB through NCBI
Molecular Modeling DataBase (MMDB)
Cn3D (“see in 3D” or three dimensions):
structure visualization software
Vector Alignment Search Tool (VAST):
view multiple structures
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Fig. 9.15
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Fig. 9.15
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Fig. 9.16
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Fig. 9.16
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Fig. 9.16
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Fig. 9.16
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Fig. 9.16
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Fig. 9.17
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Access to structure data at NCBI: VAST
Vector Alignment Search Tool (VAST) offers a variety
of data on protein structures, including
-- PDB identifiers
-- root-mean-square deviation (RMSD) values
to describe structural similarities
-- NRES: the number of equivalent pairs of
alpha carbon atoms superimposed
-- percent identity
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Many databases explore protein structures
SCOP
CATH
Dali Domain Dictionary
FSSP
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Structural Classification of Proteins (SCOP)
SCOP describes protein structures using a
hierarchical classification scheme:
Classes
Folds
Superfamilies (likely evolutionary relationship)
Families
Domains
Individual PDB entries
http://scop.mrc-lmb.cam.ac.uk/scop/
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Class, Architecture, Topology, and
Homologous Superfamily (CATH) database
CATH clusters proteins at four levels:
C Class (a, b, a&b folds)
A Architecture (shape of domain, e.g. jelly roll)
T Topology (fold families; not necessarily homologous)
H Homologous superfamily
http://www.biochem.ucl.ac.uk/basm/cath_new
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SCOP statistics (September, 2005)
Class
All a
All b
a/b
a+b
…
Total
# folds
218
144
136
279
945
a/b = parallel b sheets
a+b = antiparallel b sheets
# superfamilies
376
290
222
409
1539
# families
608
560
629
717
2845
Table 9-4
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Fig. 9.23
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Fig. 9.24
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Fig. 9.25
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Fig. 9.25
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Fig. 9.26
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Fig. 9.27
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Fig. 9.28
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Dali Domain Dictionary
Dali contains a numerical taxonomy of all known
structures in PDB. Dali integrates additional data
for entries within a domain class, such as secondary
structure predictions and solvent accessibility.
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Fig. 9.29
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Fig. 9.30
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Fig. 9.30
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Fig. 9.30
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Fold classification based on structure-structure
alignment of proteins (FSSP)
FSSP is based on a comprehensive comparison of
PDB proteins (greater than 30 amino acids in length).
Representative sets exclude sequence homologs
sharing > 25% amino acid identity.
The output includes a “fold tree.”
http://www.ebi.ac.uk/dali/fssp
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Fig. 9.31
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FSSP: fold tree
Fig. 9.32
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Fig. 9.33
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Fig. 9.34
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Approaches to predicting protein structures
There are about >20,000 structures in PDB, and
about 1 million protein sequences in SwissProt/
TrEMBL. For most proteins, structural models
derive from computational biology approaches,
rather than experimental methods.
The most reliable method of modeling and evaluating
new structures is by comparison to previously
known structures. This is comparative modeling.
An alternative is ab initio modeling.
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Approaches to predicting protein structures
obtain sequence (target)
fold assignment
comparative
modeling
ab initio
modeling
build, assess model
Fig. 9.35
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Comparative modeling of protein structures
[1] Perform fold assignment (e.g. BLAST, CATH, SCOP);
identify structurally conserved regions
[2] Align the target (unknown protein) with the template.
This is performed for >30% amino acid identity
over a sufficient length
[3] Build a model
[4] Evaluate the model
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Errors in comparative modeling
Errors may occur for many reasons
[1] Errors in side-chain packing
[2] Distortions within correctly aligned regions
[3] Errors in regions of target that do not match template
[4] Errors in sequence alignment
[5] Use of incorrect templates
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Comparative modeling
In general, accuracy of structure prediction depends
on the percent amino acid identity shared between
target and template.
For >50% identity, RMSD is often only 1 Å.
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Baker and Sali (2000)
Fig. 9.36
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Comparative modeling
Many web servers offer comparative modeling services.
Examples are
SWISS-MODEL (ExPASy)
Predict Protein server (Columbia)
WHAT IF (CMBI, Netherlands)
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