OSI Protein Modeling Challenge

1. OSI Protein Modeling Challenge December 2010

2. 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. 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, Tarcevaand Lung Cancer. Become a maven of protein structure Enhance your computer skills with Jmol Protein Modeling Challenge

4. 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. 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 Protein Databank Molecule of the Month http://www.pdb.org/pdb/explore/motm.do 5

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

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 NH2-CH-COOH R 8

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 9

10. 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 10

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

12. 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 Bankhttp://www.pdb.org/pdb/home/home.do PDB Molecule of the Month features the structure and function of a different protein each monthhttp://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/alphabetical_list.html 12

13. 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_month/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 13

14. 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 14

15. 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 15

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

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

18. 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 695-854http://www.pdb.org/pdb/explore/motm.do Must arrive at Stony Brook by 4:30 December 1 for judging 40% team score 18

19. 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 19

20. 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. 20

21. 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 21