Transcript OSI Protein Modeling Challenge

OSI Protein Modeling
Challenge
December 2010
Fall 2010
1
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
2
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
3
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
•
Good luck and have fun!
Fall 2010
4
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
5
5
Protein Structure
•
•
•
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
•
Fall 2010
s your amino acid L or D form?
6
6
D-Alanine
Fall 2010
L-Alanine
7
Amino Acids Have Unique
Chemical Characteristics
•
Each amino acid has the same “backbone” structure, but has
different chemical groups (R groups or sidechains) attached
•
Working with another team, construct an amino acid and a
dipeptide with a molymod kit
NH2-CH-COOH
R
Fall 2010
8
8
Proteins Have Secondary
Structure
•
A linear chain of amino acids is the
protein “primary” structure
•
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/
Fall 2010
9
9
Proteins Fold Into a Tertiary
Structure
•
Protein folding is due to the behavior of different chemical
groups on amino acids in an aqueous environment
•
You can explore amino acid sidechain chemistry and protein
structure through the game Fold It: http://fold.it/portal/
Fall 2010
10
10
Proteins Fold Into a Tertiary
Structure
•
Proteins spontaneously fold into a specific three dimensional
“tertiary” structure that governs a protein’s function
Fall 2010
11
11
Protein Data Bank
•
The 3-dimensional structure of proteins is often determined
by x-ray diffraction or NMR analysis
•
PDB file lists the X, Y, Z coordinates for each atom in a
protein
•
Protein Data Bank http://www.pdb.org/pdb/home/home.do
•
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
Fall 2010
12
12
Molecule of the Month (MOM)
•
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
–
Describes protein function
–
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
13
13
Jmol
•
•
•
•
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
14
14
Exploring Protein Structure
with Jmol
•
Jmol allows you to identify elements of protein structure
–
Helix (magenta)
–
Sheet (yellow)
–
N-terminus (blue)
–
C-terminus (red)
–
Amino acid sidechains (CPK)
–
Alpha-carbon backbone model format
Fall 2010
15
15
Mini-Toober Models (cont.)
•
Mark location of structures on Mini-Toober
•
Fold Mini-Toober into a 3D model representing protein
Fall 2010
16
16
Protein Modeling Challenge
•
2010 Event Rules
www.stonybrook.edu/cesame
•
Pre-build model (40%)
•
On-site build (30%)
•
Written exam (30%)
Fall 2010
17
17
EGFR Pre-Built Model 2010
•
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
–
–
Must arrive at Stony Brook by 4:30 December 1 for judging
40% team score
Fall 2010
18
18
Written Exam 2010
•
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:
•
•
•
PDB file, abstract,
Molecule of the Month
30% team score
Fall 2010
19
19
EGFR
•
•
•
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.
Fall 2010
20
20
Protein Modeling Challenge With
National Science Content Standards
•
Science and Technology
–
–
•
Abilities of Technological Design
Understandings about Science and Technology
Life Science
– The Cell
– Physiology
• Science as Inquiry
–
Abilities Necessary to do Scientific Inquiry
• Physical Science
–
–
Structure and Properties of Matter
Chemical Reactions
Fall 2010
21
21