Structural Bioinformatics Resources

1. Dr. M. Kamran Azim
H.E.J. Research Institute of Chemistry,
International Center for Chemical and Biological Sciences,
University of Karachi,
Karachi
Chem-727 (Bioinformatics)
Lecture-23
Structural Bioinformatics Resources

2. 2
What is Structural Bioinformatics?
• Structural bioinformatics refers to the analysis of
macromolecular structure particularly proteins, using
computational tools and theoretical frameworks.
• The process of predicting the 3D structures of proteins from
comparison of sequence alignments, secondary and tertiary
structure prediction, experimental structural biology data.

3. 3
Techniques in Structural Bioinformatics
• Structural Bioinformatics DBs (PDB, SCOP, CATH)
• Molecular visualization (RasMol, SwissPDB viewer)
• Protein structure prediction
Secondary structure prediction (PHD, PSIPRED)
Tertiary structure prediction
Homology modeling (Modeller, Composer)
Fold Recognition (Genthreader, TOP)
Ab initio structure Prediction (Robetta)
• Protein-protein Interaction prediction (Rosetta)
• Protein structure comparison (DALI)
• Protein structure classification (SCOP, CATH)
• Molecular docking (Dock, FlexX)

4. Structural Bioinformatics DBs
• Databases storing 3D structural information obtained
from experimental techniques (Crystallography, NMR,
Electron microscopy) of proteins, DNA, RNA, viruses,
carbohydrates, lipids and others.
• Protein DataBank [PDB]
– (premier macromolecular structure DB; www.rcsb.org)
• PDBsum (www.ebi.ac.uk/thornton-srv/databases/pdbsum)
• Structural Classification of Proteins [SCOP]
– (scop.mrc-lmb.cam.ac.uk/scop)
• CATH database (www.cathdb.info/index.html)
• Cambridg Structural DB [CSD at the CCDC]
– (contains 3D structural information of small molecules; www.ccdc.cam.ac.uk)

5. Techniques for Molecular Structural Determinations
Macromolecular Crystallography

6. Xray-Diffractometer

7. Electron density maps→atomic coordinates sets
atomic coordinates sets (x,y,z coordinates of every
atom of molecule) in text file.

8. PDB
• A repository for the 3-D structural data of large biological
macro-molecules, such as proteins, nucleic acids and viruses.
• The data obtained by X-ray crystallography or NMR
spectroscopy and submitted to PDB by scientists from around
the world, and can be accessed at no charge on the internet.
• Each structure submitted to PDB receives a four-character
alphanumeric identifier, its PDB-ID; e.g. 1ACE, 1M43
• The file formats used by the PDB;
– The PDB file format (file extension pdb or ent). This format has 80
characters per line.
– The "macromolecular Crystallographic Information file" format, mmCIF.
– An XML version of this format, called PDBML, was described in 2005.
– The structure files can be downloaded in any of these three formats.

9. PDB holdings list
(March 2009; update weekly)

10. The Cambridge Structural Database
The world repository of small molecule crystal structures
• The CSD records bibliographic, chemical and crystallographic information
for organic molecules and metal-organic compounds;
– whose 3D structures have been determined using X-ray diffraction and
neutron diffraction.
• The CSD records results of: single crystal studies and powder diffraction
studies
– which yield 3D atomic coordinate data for at least all non-H atoms.
• The CSD includes crystal structure data arising from publications in the
open literature and private Communications to the CSD (via direct
data deposition).