Transcript ppt

PROTEINS AS MATRICES
Gevorg Grigoryan, PhD
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…
folding
function
Background: Protein Structure

Secondary structure:
 common
-helices
local structural motifs
-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)
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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

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
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