Protein Modeling
Glen Cochrane
Half Hollow Hills
CRYSTAL STRUCTURE OF THE COMPLEX OF XIAP-BIR2 AND CASPASE 3 (pdb1i3o)
The Protein Modeling event is comprised of three parts:
(1)a pre‐build (40% of the score)
(2)on‐site build (30% of the score)
(3)on‐site exam (30% of the score)
Center for BioMolecular Modeling (CBM) website
(http://cbm.msoe.edu/stupro/so/index.html )
Major resource for protein biochemistry, modeling proteins and about
these specific proteins and how they play a role in the regulation of
apoptosis and the connection to this rare disease.
Objective of this presentation is to assist coaches to
prepare their team.
1.Know the principles of protein biochemistry
2.Acquire resources and learn the specifics of this year’s
protein.
3.Instructions to build the models.
4.Practice Jmol software
5.Extract information from pdb files.
6.Prepare five double sided pages of notes.
Protein Basics:
Proteins are macromolecules
Amino acids are the basic building blocks of proteins
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Amino Acids are classified by properties: polar, nonpolar,
and charged (ionic)
Polypeptides are constructed by condensation reactions
with amino acids
Protein function depends on
specific conformation (shape)
There are four levels of protein
structure.
The primary structure is the
linear sequence of amino acids.
What determines this sequence?
Where in the cell are amino acids
joined this way?
The secondary structure of
protein depends on hydrogen
bonding between C=O and NH groups.
Alpha Helix and Beta Pleated
sheets
Tertiary structure is determined by the interactions
between the side chains (R groups)
List these types of
interactions and
which ones are
weak or strong
Quaternary structure is the overall protein structure
resulting from combinations of polypeptide subunits
Resources and learn the specifics of this year’s protein.
Besides the protein basics, this is key to the written exam
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August 2004 Molecule
of the Month by David Goodsell
Look for additional references in articles and onlline about
Caspases
2012 Protein Modeling Event will focus on the XIAP and other
proteins involved in the regulation of cell death.
Caspases have been termed "executioner" proteins for apoptosis.
XIAP is an inhibitor of apoptosis protein that binds to, and inhibits,
caspase–3. When XIAP is bound to caspase–3, the protease is not
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active.
Pre-Built Model:
•Based on chains A and B of the 1i3o.pdb file
•Impounded an hour before the competition begins.
•Model is built at a scale of 2cm/amino acids.
•Chain A is 143 amino acids Mini-Toober is 286cm.
•Chain B is 101 amino acids Mini-Toober is 202cm.
Creative additions Must demonstrate function:
•Interaction with other molecules
•Zinc fingers
•Ligands
•Significant side chains
Could be 20% of score
Include 3X5 card with team and explain additions
Common Mistakes
•Blue cap/red cap in wrong position
•N-terminus, or the beginning of the protein, is the BLUE cap and
C-terminus, or the end of the protein, is the RED cap
•Missing secondary structures
•Model has 3 helices, and it should have 4 (or vice versa)
•Left-handed helices
•Tertiary structure is incorrect
•Protein should be globular and it is flat
•Creative additions on the prebuild are inappropriate
•Incorrect sidechains
•Too much information (all of the sidechains)
•Onsite amino acids are positioned incorrectly
•In the wrong spot (position 49 rather than 59)
•Amino acids are pointing in the wrong direction (should be
pointing to the center of the protein and it is facing outward)
Prebuild Kit
http://www.3dmoleculardesigns.com/scienceolympiad.asp
Instructions to build the models
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Use the CBM website for the video instructions
On-Site Build: No on-line resources, file will be loaded
on the computer. Bring 10 pages (5 sheets) of info.
Jmol
Teams are expected to understand the Jmol
protein visualization tools. These online tools
will be necessary for construction of both the
Pre-build and the On-site build.
Jmol: an open-source
Java viewer for
chemical structures in
3D
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http://cbm.msoe.edu/includes/pdf/JmolQuickReferenceSheet.pdf
Common Commands:
Restrict*A (removes all
but chain A)
Restrict*A,*B (removes
all but A and B)
PRACTICE
Take a look at the
protein using Jmol
Go to www.pdb.org
Search: 1i3o
The Protein Data Bank (PDB) is a repository for the 3-D
structural data of large biological molecules, such as
proteins and nucleic acids.
Obtained by X-ray crystallography or NMR spectroscopy.
Submitted by biologists and biochemists from around the
world.
How to display pdb file from pdb.org
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Regionals: Selected region
of XIAP (1i3opdb)
States: Selected region of
PARP (3od8.pdb)
The On-Site Exam (30% of a team’s final score)
•Combination of multiple choice and short answer questions
•Can bring 10 pages of notes (No internet)
•Topics include
•Basic chemistry questions regarding atoms, bonds, and
reactions
•Basic protein structure
•Structure/function relationship questions
•Specific protein questions (related to prebuilt and onsite build
proteins)
Past Exams: http://cbm.msoe.edu/stupro/so/SONTExamRubric.html
Protein Modeling
Teams of 3
(only 2 at state competition).
Prepare using CBM website.
Superior event incorporating the tools used by scientists,
on-line resources, communication, cooperation, delegation
of responsibilities, …