Protein Modeling ChallengeScience Olympiad Trial Event

Shannon Colton, Ph.D., Event SupervisorGary Graper, Event Technical Advisor

Protein Modeling Challenge

• To compete successfully in the Protein Modeling Challenge, you will:

– Identify basic features of protein structure

– Explore protein structure with the computer visualization program Jmol

– Create physical models using the flexible modeling media, Mini-Toobers

2

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!

3

Protein Structure• Proteins are macromolecules

• Amino acids are the basic building blocks of proteins

4

Nitrogen

Amino Group

Carboxyl Group

Alpha-Carbon

Sidechain (R-Group)

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 (www; this link will bring you to a webpage that has multiple pdfs pertaining to protein structure at the bottom of the page)

– Collection of models and activities: Introduction To Protein Structure (ITOPS) (www)

– MSOE Model Lending Library(www)

5

Amino Acids Have Unique Chemical Characteristics

• Each amino acid has the same “backbone” structure, but has different chemical groups (R groups or sidechains) attached

• Construct an amino acid and a dipeptide with a molymod kit (ITOPS)(pdf)

6

NH2-CH-COOH

R

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: beta-sheet or alpha-helix

• Construct an alpha-helix and beta-sheet activity (ITOPS, Introduction To Protein Structure)

(pdf)

7

Alpha Helix

Beta-sheet

Proteins Fold Into a Tertiary Structure

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

8

Proteins Fold Into a Tertiary Structure

• Protein folding is due to the behavior of different chemical groups on amino acids in an aqueous environment

• Explore amino acid sidechain chemistry and protein folding with the Amino Acid Starter Kit Activity (ITOPS, Introduction To Protein Structure)(pdf)

9

Defining Protein Structure• The 3-dimensional structure of proteins is often determined by x-ray diffraction or

NMR analysis

• Each atom in a protein is assigned a specific set of X, Y, Z coordinates in 3D space to create a PDB data file

10

Protein Data Bank

• PDB file lists the X, Y, Z coordinates for each atom in a protein

• Protein Data Bank website is the location to download PDB files(www)

• PDB Molecule of the Month features the structure and function of a different protein each month(www)

11

Molecule of the Month (MOM)• A monthly PDB feature written by David Goodsell

– Features a specific molecule

– Describes protein function

– Relates structure with function

12

RibonucleasesSeptember 2008

Molecule of the Month(www)

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

• We will use this website on the day of competitions.

13

RasMol versus Jmol• Many of you may be familiar with RasMol. RasMol is a great program and may be

continued to be used by Science Olympiad Teams. However, since there have not been updates to RasMol to allow for it to operate easily on Macs, Jmol will be the computer visualization program to be used in the future.

• The commands that you have used in RasMol are almost the same in Jmol.• You may practice using Jmol by using the this website.

14

Exploring Protein Structure with Jmol

• Jmol allows you to identify elements of protein structure

– Helix (magenta)

– Sheet (yellow)

– N-terminus (or first amino acid in the protein(blue)

– C-terminus (or the last amino acid in the protein)(red)

– Amino acid sidechains (CPK)

– Alpha-carbon backbone model format

15

Jmol Resources• Use the following resources as tools in learning Jmol:

– Jmol free download(www)

– Alternatively, use the same website that will be used on the day of the competition (www)

– Assistance on downloading and installing Jmol on your computer (pdf)

– Reference Card of Jmol commands, condensed(www)

16

Jmol Exercises

• Explore the structure of a zinc finger domain and beta-globin proteins and practice RasMol

– Zinc Finger Exercise (www) Answers (www)

– Beta Globin Exercise (www)Answers (www)

17

Mini-Toober Models• Mini-Toobers are a flexible modeling media

• Developed by 3D Molecular Designs (3DMD) with a Small Business Initiative Research grant (SBIR) from the National Science Foundation (NSF)(www)

18

Create Physical Mini-Toober Models

• Identify protein structural features using Jmol (ie: helix, sheet)

• Identify important amino acid sidechains that play a significant role in the function of the protein– This can be accomplished by exploring the story

of the protein– David Goodsell’s Molecule of the Month is a

great place to start

19

Mini-Toober Models (cont.)• Mark location of structures on Mini-Toober using a marker or pen

• Fold Mini-Toober into a 3D model representing protein based on the image you created using Jmol

20

Example Protein:Zinc Finger Protein

• Zinc finger proteins bind DNA

• A zinc finger domain contains a short alpha-helix, 2 beta-strands and conserved Cys, His amino acids that bind a molecule of zinc

• For more information about the zinc finger protein, you can read David Goodsell’s Molecule of the Month (www)

21

Zinc Finger Folding Exercise

• Zinc Finger Folding Activity is available from MSOE Lending Library– This activity will allow you to fold a toober into a zinc finger to

practice modeling proteins (www)

• Challenge: Download the 1ZAA pdb file, create an image in Jmol, identify key structural features, and fold a Mini-Toober model

22

Protein Modeling ChallengeScience Olympiad Trial Event

• 2009 Event Rules (www)

• Protein Modeling Event– Pre-build model (40% of total score)– On-site build (30% of total score)– Written exam (30% of total score)

23

Protein Modeling 2008Prebuild

• The 2008 Protein Modeling Event focused on the calcium-binding protein – Calmodulin, described in the August 2003 Molecule of the Month (www)

• Teams constructed a model of the entire calmodulin protein for the prebuild

Prebuild Rubric (pdf) – 40% of the final score

24

Protein Modeling 2008 Onsite Builds

• For onsite competitions, selected regions of the calmodulin were modeled

Regional Onsite Build Rubric (pdf) – 30% of the regional final score

State Onsite Build Rubric (pdf) – 30% of the state final score

25

Protein Modeling 2008 Exam

• Teams also completed an exam based on protein structure and specifically on the function of calmodulin

2008 State Exam (pdf) – 40% of final score

26

National Science Content Standards

• Science and Technology– Abilities of Technological Design– Understandings about Science and Technology

• Life Science– The Cell

• Science as Inquiry– Abilities Necessary to do Scientific Inquiry

• Physical Science– Structure and Properties of Matter– Chemical Reactions

• Detailed Alignment(www)

27

PDB Newsletter Features Protein Modeling

• PDB Newsletter, No. 26, Summer 2005 (www)

• PDB Newsletter, No. 33, Spring 2006(www)

• PDB Newsletter, No. 36, Winter 2008(www)

• PDB Newsletter, No. 38, Summer 2008(www)

28

Protein Modeling Supports Science Olympiad Mission

• Emphasis on teamwork

29

Protein Modeling Supports Science Olympiad Mission

• Provides curriculum training workshops and web based distribution of materials from the MSOE Center for BioMolecular Modeling web site(www)

30

Protein Modeling Supports Science Olympiad Mission

• Brings science to life, shows how science works, emphasizes problem solving aspects and understanding of concepts

31

Protein Modeling Supports Science Olympiad Mission

• Promotes partnerships among community, businesses, industry, and education

32

Protein Modeling Supports Science Olympiad Mission

• Promotes high level of achievement and demonstrates students can perform at levels approaching practicing scientists

33

CBM Programs• Teacher Professional Development (www)

– Genes, Schemes, Molecular Machines – Modeling the Molecular World– Molecular Stories of Research-Based Health Care

• SMART Teams (Students Modeling A Research Topic)(www)

• MSOE Model Lending Library(www)

• Science Olympiad Protein Modeling Challenge(www)

34

Additional Information• For more information, or to ask questions, please contact:

Shannon Colton, Ph.D., colton@msoe.edu or 414-277-2824

35

http://cbm.msoe.edu