Structural genomics

This presentation give brief idea about strutural genomics

1. Structural genomics By: Vaibha v Kumar Maurya

2. What is genomics? Genomics is the molecular characterization of whole genomes.

3. Structural genomics It characterizes the physical nature of whole genome. It includes the genetic mapping, physical mapping and sequencing of whole genomes. It describes the 3D structure of every protein encoded by a given genome.

4. Diff b/w str genomics & traditional str prediction Structural genomics attempts to determine the structure of every protein encoded by the genome. Traditional structure prediction focuses on one particular protein .

5. ADVANTAGES Economy of scale Scientific community gets immediate access to new structure as well as to reagents such as clones & proteins.

6. DISADVANTAGES Many of the structure of protein are of unknown function & don’t have corresponding publication. It requires new ways of communicating the str information to the broader research community.

7. GOALS To identify novel protein folds : Done by ab -initio modeling. Protein 3D structure determination : -3D structure knowledge is important to understand the function of protein. -It is also used in drug discovery and protein engineering.

8. full structural coverage of a simple model organism

9. METHODS Structural genomics takes advantage of completed genome sequence in order to determine protein structure. The gene sequence of the target protein can be compared to a known sequence & structure information can be inferred from known protein structure. Structure genomics can be used to predict novel protein folds based on other structural data. It also uses modeling based approach that relies on homology b/w the unknown protein & a solved protein.

10. Structural Genomics Method Development Discovery of New Folds

11. De novo method Completed genome sequence allows every ORF to be cloned & expressed as protein. The proteins are then purified and crystallised Then subjected to str determination: X-ray crystallography & NMR The whole genome sequence allows for the design of every primer required in order to amplify all the ORFs, clone into bacteria and express them This whole genome approach allows for structure determination of every protein that is encoded by the genome.

12. MODELING BASED METHOD 1. AB-INITIO METHOD: This approach uses protein sequence data & the chemical & physical interaction of the encoded amino acid to predict 3D str of protein with no homology to solve protein structure. Rosetta program : highly successful method It divides protein into short segment and arranges short polypeptide chain into a low energy local conformation. Available for commercial use and for non commercial use Robetta is used.

13. 2. SEQUENCE BASED MODELING This method compares the gene sequence of an unknown protein with sequence of protein with known structure. Depending on degree of similarity b/w the sequence the str of known protein can be used as model for solving the str of unknown protein.

14. 3. THREADING It is based on fold similarities rather than sequence identity. This method is used to identify distantly related protein & can be used to infer molecular functions.

15. EXAMPLES 1. Mycobacterium tuberculosis  proteome -The goal of the  TB Structural Genomics Consortium  is to determine the structures of potential drug targets in  Mycobacterium tuberculosis , the bacterium that causes tuberculosis. - The development of novel drug therapies against tuberculosis are particularly important given the growing problem of  multi-drug-resistant tuberculosis .

16. 2. The  Thermotogo maritima  proteome One current goal of the  Joint Center for Structural Genomics  (JCSG), a part of the  Protein Structure Initiative  (PSI) is to solve the structures for all the proteins in  Thermotogo maritima , a thermophilic bacteria. -  T. maritima  was selected as a structural genomics target based on its relatively small genome consisting of 1,877 genes and the hypothesis that the proteins expressed by a thermophilic bacterium would be easier to crystallize.

17. Protein Structure Databases and Classification Protein bank  (PDB): repository for protein sequence and structural information UniProt : provides sequence and functional information Structural Classification of Proteins  (SCOP Classifications): hierarchical-based approach Class, Architecture, Topology and Homologous superfamily  (CATH): hierarchical-based approach

18. The structural genomics experimental pipeline.