1Fall 2010

OSI Protein Modeling Challenge

December 2010

2Fall 2010

Joan Kiely, Stony Brook Universityjoan.kiely@stonybrook.edu

Debbie Pelio, Stony Brook Universitycesame@stonybrook.edu

http://www.stonybrook.edu/cesame

Linda Padwa, Stony Brook UniversityKristen La Magna, Stony Brook University

Shannon Colton, Ph.D., Technical AdvisorMilwaukee School of Engineering

http://cbm.msoe.edu/

3Fall 2010

• 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

4Fall 2010

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!

5Fall 20105

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 Monthhttp://www.pdb.org/pdb/explore/motm.do

6Fall 2010

• 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?

7Fall 2010

                              

D-Alanine   L-Alanine

8Fall 20108

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

9Fall 20109

• 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

10Fall 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

11Fall 201011

• Proteins spontaneously fold into a specific three dimensional “tertiary” structure that governs a protein’s function

Proteins Fold Into a Tertiary Structure

12Fall 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.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

13Fall 201013

Molecule of the Month (MOM)

• A monthly PDB feature written by David Goodsellhttp://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

14Fall 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

15Fall 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

16Fall 201016

Mini-Toober Models (cont.)• Mark location of structures on Mini-Toober

• Fold Mini-Toober into a 3D model representing protein

17Fall 201017

Protein Modeling Challenge

• 2010 Event Rules www.stonybrook.edu/cesame

• Pre-build model (40%)

• On-site build (30%)

• Written exam (30%)

18Fall 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 695-854http://www.pdb.org/pdb/explore/motm.do

– Must arrive at Stony Brook by 4:30 December 1 for judging– 40% team score

19Fall 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

20Fall 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.

21Fall 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