Protein structure databases

• Contain the spatial coordinates of macromolecules whose 3D structure has

been obtained by X-ray or NMR studies

• Proteins represent more than 90% of available structures (others are DNA,
RNA, sugars, virus, complex protein/DNA…)

• PDB (Protein Data Bank), SCOP (structural classification of proteins

(according to the secondary structures)), BMRB (BioMagResBank; RMN
results)

2
 Challenges

 Fast growth in
number of structures
 Growing
complexity of
depositions
 Greatly expanded
user community

Year
3
 State of the PDB

• ~25,000 released structures in the PDB archive

• Over 7,000 new structures deposited in 2003
• ~200,000 file downloads per day

Depositions by Macromolecule Type:

• 92.5% Protein
• 3.5% Nucleic acid
• 4% Protein-nucleic acid complexes

Depositions by Experiment
• 85.7% X-ray
• 13.7% NMR
• 0.4% CryoEM
• 0.2% Other

4
 Integrated Deposition, Processing, and
Validation

• Built on top of the mmCIF dictionary

• web interface AdIt
– Customization:
• Level of annotation (deposition/annotation)
• Experimental type (X-ray/NMR)
• Integrated validation server: maxit, AdIt, validation
• The whole PDB functionality available from the web
• data are validated by curators (syntactic correctness, scienific correctness,
e.g. checking of sequences), they use internal mmCIF with special
categories
• generating of official mmCIF and PDB files, they are uploaded to given
directories
• at the same time, mmCIF is converted into SQL query, that is sent to DB2
database system

5
 How the Data Flow in and Out of PDB

2 Annotate
Validation Report
1 Deposit
PDB ID
Archival
of Data
Depositor PDB
ADIT Annotate Validate Distribution
Entry
Core Site
3 Correct DB
Corrections

4 Approve

Depositor Approval

6
• PDB ID – model – chain – residue – atom

7
 Data formats

• PDB
– model, chain, residue, atom
– http://www.pdb.org/docs.html
• mmCIF
– archival format of PDB
– http://mmcif.pdb.org/
• pdbML
– blind transcription of mmCIF to XML, just to be cool and in

8
 PDB Format

 a legacy format;

 incomplete and not structured enough to describe objects as

complicated as molecules;

 its limits have been broken several times;

 understood by most programs.

9
 Integration of Other Resources
3D Domain CATH
Primary References Structure
Derived References Assignments SCOP

Data curation

Source SWISS-PROT/ PubMed Enzyme

Organism GenBank IDs Classification

NCBI KEGG Enzyme

Taxonomy Pathways

Gene Ontology Genomes Structural Genomics

(NCBI LocusLink) Targets

OMIM/Disease GeneCards SNPs

Re-engineered Database 10
 Site Navigation

Persistent Keyword Search Box

New User Help

PDB Static
Site Search Context-
sensitive
Persistent Help
Navigation
Bar with User
Session History

11
 Browse Tools
Structure data categorized and presented
through several browsers

Gene
Ontology

Enzyme
Classification

Taxonomy

Disease

Ligands

CATH/SCOP
12
 PDB Archive Search Tools
SearchLite, StatusSearch & QuickSearch
SearchFields – query specific mmCIF fields
Query Review
and Refinement

Title, Deposition/
Release Dates

X-Ray & NMR

Experimental
Details

Secondary Citation,
Structure GO, EC, Source, Database
& Geometry Ligands, Sequence References

13
 Query Results Page
Order Results by Resolution/Deposition Date/PDB ID
Downloads
Navigation to Query/Results
(PDB/mmCIf/XML)

Detailed Tabular
Reports

Save
Report as
Excel

Order Results by
Column Values
14
 Structure Summary Page
Customized Summary for X-Ray and NMR Structures
Navigation Print PDF
‘Bread Crumbs’
to Results Page Toggle –
Asymmetric/
Downloads, Biological
Reports, Viewers, Unit Images
External links
Simple,
User-Friendly
Pubmed Abstract 3D Viewers
Search
Ligand
SCOP, CATH Viewer
and GO –Listing Ligand-
and Search Structure
Interaction
Viewer 15
 New Detailed Reports

Biology & Chemistry Materials &

Methods

Structural Features

16
 MMDB

• NCBI's structure database is called MMDB (Molecular

Modeling DataBase), and it is a subset from the Protein Data
Bank (PDB), excluding theoretical models.

• MMDB is a database of ASN.1-formatted records. It was

designed for flexibility, and as such, is capable of archiving
conventional structural data as well as future descriptions of
biomolecules, such as those generated by electron
microscopy (surface models).

17
 Searching MMDB

• The structure database may be queried directly, using specific fields

such as author names, or text terms occurring anywhere in the
structure description.

• Alternatively you can use a PDB 4-character code or a numerical

MMDB-Id to retrieve structure summary pages directly

18
19
 Molecular Visualization

• Cn3D - uses MMDB-Entrez’s structure database

http://www.ncbi.nlm.nih.gov/Structure/CN3D/cn3d.shtml
• RasMol http://www.umass.edu/microbio/rasmol/
• Protein Explorer
http://www.umass.edu/microbio/rasmol/rotating.htm
• OpenRasMol http://www.openrasmol.org/
• MolviZ.org http://www.umass.edu/microbio/chime
• World Index of Molecular Visualization
http://molvis.sdsc.edu/visres/index.html
20
 Molecular Visualization

SimpleViewer built
using the Java 3D
based Molecular
Biology Toolkit
(MBT: mbt.sdsc.edu)

Ligand Interaction Viewer built

using MBT – view hydrophilic and
hydrophobic interactions between
the ligand and neighboring
residues in the structure
21