Structural Genomics

1
Structural Genomics

• Leader Remarks
• Maricel Kann
• NCBI
• National Institutes of Health

2
Proteins
Sequence (primary structure)
Better understanding of the cell
mechanism. Increasing the possibility to develop
new drugs and therapies cure diseases Improve
quality of life
Secondary Structure (alpha helix, beta sheet,
etc)
Tertiary Structure (side chain packing in 3-D
structure)
Quaternary Structure (association of those
subunits)
Protein Function
3
Protein Sequence

• MRAAVVYKTDGHVKRIEEALKRLEVEVELFNQPSEELENFDFIVSVGGDG
  TILRILQKLKRCPPIFGINTGRVGLLTHAS PENFEVELKKAVEKFEVER
  FPRVSCSAMPDVLALNEIAVLSRKPAKMIDVALRVDGVEVDRIRCDGFIV
  ATQIGSTGYAF SAGGPVVEPYLECFILIPIAPFRFGWKPYVVSMERKIE
  VIAEKAIVVADGQKSVDFDGEITIEKSEFPAVFFKNEKRFRN
  LFGKVRSIG

4
(No Transcript)
5
Protein 3-D structure

• Build homology models.
• By mapping residues to the known structures we
  can infer binding sites.
• Dock ligands to these binding sites.
• Infer function of new sequences through
  comparison to other proteins
• For this transfer of annotation from known
  proteins, it is key to have good set of correctly
  classified proteins for which in turn is key to
  have 3D-structure.

6
Protein 3-D structure

• The information for protein classification can
  come from protein conserved regions with defined
  structure .
• Alternatively, as shown by Anna Panchenko in this
  section, one can extract such information from
  non-conserved regions or loops.
• Just a reminder, though, 3-D structure is a
  static picture but proteins are flexible and need
  to change their shape in order to perform their
  functions (disorder in proteins will also be
  addressed at this conference by Keith Dunker).

7
Protein-protein Interactions

• Furthermore, proteins interact among themselves
  and understanding such interactions is the key to
  revealing most of the cell mechanisms.
• If the 3-D structure of these protein complexes
  is available, the protein interaction surface can
  be characterized and the interaction better
  understood.
• In this section Julie Bernauer, explores
  refinements of the protein-protein docking tools
  and Teresa Przytycka looks into the interaction
  networks from the perspective of graph theory.

8
PDB

• Protein Databank.
• Is the repository for the processing and
  distribution of 3-D biological macromolecular
  structure data.
• Phil Bourne along with Dr. Berman are among the
  leaders of this project

9
Over 30,000 protein structures as today.
10
Structural Genomics Initiative

• Structural genomics is a worldwide initiative
  aimed at quickly determining a large number of
  protein structures using X-ray crystallographic
  and NMR technologies. These structures are being
  determined in a high throughput mode as the study
  of protein structure is central in molecular
  biology and in the understanding of disease.

11
Questions

• Many questions arise as we see the increasing
  number of sequences in PDB.
• Our next speaker, Phil Bourne is addressing
  several questions, for instance since the
  ultimate challenge is to understand function and
  cure or understand the cause of diseases what is
  the coverage in terms of disease and function of
  these structures?

12
Structural Genomics

• Phil Bourne University of California San Diego.
  USAFunctional Coverage of the Human Genome by
  Existing Structures, Structural Genomics Targets
  and Homology Models
• Julie Bernauer, Yeast Structural Genomics - IBBMC
  UMR. FranceA new Protein-Protein Docking Scoring
  Function Based on Interface Residues Properties
• Teresa Przytycka National Institutes of Health.
  NCBI. USA Genomics meets Graph Theory
• Anna Panchenko, National Institutes of Health.
  NCBI. USAEvolution of protein structures
  Analysis of Protein Loops

13

• THANKS to Willy Valdivia