Gevorg Grigoryan, PhD

PROTEINS AS MATRICES

Background: Cells Nano-Machines Cells are tiny machines:

sense environment, respond, make decisions move, search for food (example) synthesize chemicals make copies of themselves

Cellular macromolecules: e.g. proteins workhorses of the cell responsible for many of these tasks

Background: Proteins

Primary structure: chains of amino acids 20 amino acids:

aka “residues” different in side-chain polar/hydrophobic acidic/basic large/small

Background: Protein Structure Amino-acid sequence defines the full

molecular structure of the protein and ultimately its function:

…AKWLMENI… function

folding

Background: Protein Structure Secondary structure:

common local structural motifs

-helices -sheets

Background: Protein Structure Tertiary and Quaternary structure:

Nowadays, much more data… Protein Data Bank (PDB):

www.pdb.org – available to anyone for free as of Jan 25, 2011 at 4 PM there are 70,813

Structures

Protein Structural Universe

Protein Structural Universe

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

Representation: Distance Maps A good representation of structure is

key:

Search

Search Method

Mapping of Distances for the Characterization of Topology (MaDCaT)

Search Method

Mapping of Distances for the Characterization of Topology (MaDCaT)

1

2

3

1 2 3

1

2

3

Search Method

Mapping of Distances for the Characterization of Topology (MaDCaT)

Search Method: branch and bound Mapping of Distances for the

Characterization of Topology (MaDCaT)

Search Method: branch and bound Mapping of Distances for the

Characterization of Topology (MaDCaT)

Search Method: branch and bound Mapping of Distances for the

Characterization of Topology (MaDCaT)

Search Method: branch and bound Mapping of Distances for the

Characterization of Topology (MaDCaT)

Search Method: Result

Mapping of Distances for the Characterization of Topology (MaDCaT)

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