1. Gevorg Grigoryan, PhD PROTEINS AS MATRICES

2. Background: Cells  Nano-Machines  Cells are tiny machines:  sense environment, respond, make decisions  move, search for food (example)example  synthesize chemicals  make copies of themselves  Cellular macromolecules:  e.g. proteins  workhorses of the cell  responsible for many of these tasks

3. Background: Proteins  Primary structure:  chains of amino acids  20 amino acids: aka “residues” different in side-chain polar/hydrophobic acidic/basic large/small

4. Background: Protein Structure  Amino-acid sequence defines the full molecular structure of the protein and ultimately its function: …AKWLMENI… function folding

5. Background: Protein Structure  Secondary structure:  common local structural motifs  -helices  -sheets

6. Background: Protein Structure  Tertiary and Quaternary structure:

7. Nowadays, much more data…  Protein Data Bank (PDB):  www.pdb.org – available to anyone for free www.pdb.org  as of Jan 25, 2011 at 4 PM there are 70,813 Structures

8. Protein Structural Universe

9.  Questions about the Universe of Protein Structure:  What is the universe? Where are the building blocks?  Are there functions specific to certain fragments?  Can we design new structure/functions from building blocks?  Need:  convenient representation of structure  efficient search and classification methods

10. Representation: Distance Maps  A good representation of structure is key:

11. Search

12. Search Method  Mapping of Distances for the Characterization of Topology (MaDCaT)

13. Search Method  Mapping of Distances for the Characterization of Topology (MaDCaT) 1 2 3 123 1 2 3

14. Search Method  Mapping of Distances for the Characterization of Topology (MaDCaT)

15. Search Method: branch and bound  Mapping of Distances for the Characterization of Topology (MaDCaT)

16. Search Method: branch and bound  Mapping of Distances for the Characterization of Topology (MaDCaT)

17. Search Method: branch and bound  Mapping of Distances for the Characterization of Topology (MaDCaT)

18. Search Method: branch and bound  Mapping of Distances for the Characterization of Topology (MaDCaT)

19. Search Method: Result  Mapping of Distances for the Characterization of Topology (MaDCaT)

20. Conclusions/Future  Distance maps are a feasible way of representing and classifying protein structure  Searches for tertiary structural elements, with multiple fragments are possible  Future questions:  given any structure, decompose it into common blocks  splice common fragments together to engineer new structure  at some point efficiency is an issue, need better search approaches