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OSI Protein Modeling
Challenge
December 2010
Fall 2010
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Joan Kiely, Stony Brook University
[email protected]
Debbie Pelio, Stony Brook University
[email protected]
http://www.stonybrook.edu/cesame
Linda Padwa, Stony Brook University
Kristen La Magna, Stony Brook University
Shannon Colton, Ph.D., Technical Advisor
Milwaukee School of Engineering
http://cbm.msoe.edu/
Fall 2010
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Protein Modeling Challenge
• To compete successfully in the Protein
Modeling Challenge, you will:
– Meet and get to know Epidermal Growth
Factor Receptor (a tyrosine kinase
receptor), Tarceva and their roles in Lung
Cancer
– Build models that illustrate what you know
about EGFR, Tarceva and Lung Cancer.
– Become a maven of protein structure
– Enhance your computer skills with Jmol
Fall 2010
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Web-Based Resources
•
This powerpoint presentation will serve as an interactive resource
for your team to gain the knowledge they need to be successful in
the Protein Modeling Challenge
•
You will find links distributed throughout this presentation,
indicated by the blue underlined text
•
Follow these links to the appropriate sources
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Good luck and have fun!
Fall 2010
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Protein Structure
Resources
•
The following links will serve as tools to help you learn the
basic information needed to be successful in this challenge.
Please follow these links:
–
Basic Introduction to Protein Structure and Modeling
– http://cbm.msoe.edu/stupro/so/index.html
–
Fall 2010
Protein Databank Molecule of the Month
http://www.pdb.org/pdb/explore/motm.do
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Protein Structure
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Proteins are macromolecules
Amino acids are the basic building blocks of proteins
Working as a team, make an amino acid
Sidechain (R-Group)
Alpha-Carbon
Carboxyl
Group
Nitrogen
Amino Group
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Fall 2010
s your amino acid L or D form?
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D-Alanine
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L-Alanine
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Amino Acids Have Unique
Chemical Characteristics
•
Each amino acid has the same “backbone” structure, but has
different chemical groups (R groups or sidechains) attached
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Working with another team, construct an amino acid and a
dipeptide with a molymod kit
NH2-CH-COOH
R
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Proteins Have Secondary
Structure
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A linear chain of amino acids is the
protein “primary” structure
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A chain of amino acids will
spontaneously form stable
“secondary structures”, ie: betasheet or alpha-helix
•
•
Hydrogen bonds may stabilize these
structures
Science researchers would like to
understand what controls this
folding.
Alpha Helix
Beta-sheet
– http://fold.it/portal/
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Proteins Fold Into a Tertiary
Structure
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Protein folding is due to the behavior of different chemical
groups on amino acids in an aqueous environment
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You can explore amino acid sidechain chemistry and protein
structure through the game Fold It: http://fold.it/portal/
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Proteins Fold Into a Tertiary
Structure
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Proteins spontaneously fold into a specific three dimensional
“tertiary” structure that governs a protein’s function
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Protein Data Bank
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The 3-dimensional structure of proteins is often determined
by x-ray diffraction or NMR analysis
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PDB file lists the X, Y, Z coordinates for each atom in a
protein
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Protein Data Bank http://www.pdb.org/pdb/home/home.do
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PDB Molecule of the Month features the structure and
function of a different protein
each month
http://www.pdb.org/pdb/static.do?p=education_discussion/
molecule_of_the_month/alphabetical_list.html
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Molecule of the Month (MOM)
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A monthly PDB feature written by David Goodsell
http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_m
onth/alphabetical_list.html
–
Features a specific molecule
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Describes protein function
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Relates structure with function
Epidermal Growth Factor June 2010 David
Goodsell
http://www.pdb.org/pdb/static.do?p=education_
discussion/molecule_of_the_month/pdb126
_1.html
Fall 2010
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Jmol
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Fall 2010
Jmol is a computer visualization software that displays data
from a PDB file as a “3D” image of the molecule on the
computer screen
Jmol is Java-based and will work on most computers
http://bioportal.weizmann.ac.il/oca-docs/fgij/index.htm
http://cbm.msoe.edu/teachRes/index.html
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Exploring Protein Structure
with Jmol
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Jmol allows you to identify elements of protein structure
–
Helix (magenta)
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Sheet (yellow)
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N-terminus (blue)
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C-terminus (red)
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Amino acid sidechains (CPK)
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Alpha-carbon backbone model format
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Mini-Toober Models (cont.)
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Mark location of structures on Mini-Toober
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Fold Mini-Toober into a 3D model representing protein
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Protein Modeling Challenge
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2010 Event Rules
www.stonybrook.edu/cesame
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Pre-build model (40%)
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On-site build (30%)
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Written exam (30%)
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EGFR Pre-Built Model 2010
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Epidermal Growth Factor and written description based on June
2010 Molecule Of the Month and Protein Databank File 1M17
residues 695-854
http://www.pdb.org/pdb/explore/motm.do
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Must arrive at Stony Brook by 4:30 December 1 for judging
40% team score
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Written Exam 2010
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Exam covers material in:
– PDB file 1M17
– Molecule of the Month article on Epidermal Growth Factor
– Jmol
– Campbell, Biology, will be used a the material base for questions on
protein structure and function and cell communication
– Taken as a group
– Available at the exam will be:
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PDB file, abstract,
Molecule of the Month
30% team score
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EGFR
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On-site build
PDB file will be provided on the day of the exam
Students will build a portion of the EGFR receptor. They will be
given: a toober, selected amino acid side chains, a computer, jmol
and the pdb file.
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Protein Modeling Challenge With
National Science Content Standards
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Science and Technology
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Abilities of Technological Design
Understandings about Science and Technology
Life Science
– The Cell
– Physiology
• Science as Inquiry
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Abilities Necessary to do Scientific Inquiry
• Physical Science
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Structure and Properties of Matter
Chemical Reactions
Fall 2010
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