1. Fall 20101 OSI Protein Modeling Challenge December 2010

2. Fall 20102 Joan Kiely, Stony Brook University joan.kiely@stonybrook.edu Debbie Pelio, Stony Brook University cesame@stonybrook.edu 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/

3. Fall 20103 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 Protein Modeling Challenge

4. Fall 20104 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!

5. Fall 20105 5 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.htmlhttp://cbm.msoe.edu/stupro/so/index.html –Protein Databank Molecule of the Month http://www.pdb.org/pdb/explore/motm.do

6. Fall 20106 Proteins are macromolecules Amino acids are the basic building blocks of proteins Working as a team, make an amino acid 6 Protein Structure Nitrogen Amino Group Carboxyl Group Alpha-Carbon Sidechain (R-Group) s your amino acid L or D form?

7. Fall 20107 D-Alanine L-Alanine

8. Fall 20108 8 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 NH 2 -CH-COOH R

9. Fall 20109 9 A linear chain of amino acids is the protein “primary” structure A chain of amino acids will spontaneously form stable “secondary structures”, ie: beta- sheet or alpha-helix Hydrogen bonds may stabilize these structures Science researchers would like to understand what controls this folding. –http://fold.it/portal/ Proteins Have Secondary Structure Alpha Helix Beta-sheet

10. Fall 201010 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/ Proteins Fold Into a Tertiary Structure

11. Fall 201011 Proteins spontaneously fold into a specific three dimensional “tertiary” structure that governs a protein’s function Proteins Fold Into a Tertiary Structure

12. Fall 201012 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.dohttp://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

13. Fall 201013 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

14. Fall 201014 Jmol 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

15. Fall 201015 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

16. Fall 201016 Mini-Toober Models (cont.) Mark location of structures on Mini-Toober Fold Mini-Toober into a 3D model representing protein

17. Fall 201017 Protein Modeling Challenge 2010 Event Rules www.stonybrook.edu/cesame Pre-build model (40%) On-site build (30%) Written exam (30%)

18. Fall 201018 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 http://www.pdb.org/pdb/explore/motm.do –Must arrive at Stony Brook by 4:30 December 1 for judging –40% team score

19. Fall 201019 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

20. Fall 201020 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.

21. Fall 201021 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