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Proteins in 3D, NMC 2009
- 1. Proteins in 3D Viewing Biological Molecules in the Classroom OEIT | MIT | Star Lourdes Aleman | Molly Ruggles
- 4. User-centered tools faithful to the science foundations of the domains they represent.
- 8. Handout for downloading and installing StarBiochem
- 12. TealSim visualization: Helmholtz Coil
- 13. TEALSim --> Star Biochem Parser to interpret data from PDB Specs to render data visually Schubert & Ceraj: adapt TEALSim to other disciplines. Graham Walker: improve comprehension (Biology) Physics data: not much computation: lots Biology data: lots computation: not much
- 16. Proteins perform many important biological functions hemoglobin carry oxygen in the blood F1 ATPase generate energy antibody protect against infections aquaporin water transport microtubules cell division Protein Data Bank website
- 17. The function of a protein is determined by its structure structure function
- 20. Understanding how proteins work DNA repair proteins
- 22. Mutations often result in disease mutations cancer
- 23. Where do mutations come from?
- 24. DNA mutations can be caused by various agents cancer mutations
- 25. DNA mutations can be caused by various agents UV rays (sun) oxidation (respiration, radiation, smoking) toxic chemicals (industrial & environmental) X-rays (clinic) viruses (HPV) cancer mutations endogenous (DNA replication)
- 26. DNA mutations can be caused by various agents UV rays (sun) oxidation (respiration, radiation, smoking) toxic chemicals (industrial & environmental) X-rays (clinic) viruses (HPV) cancer mutations endogenous (DNA replication) DNA glycosylases
- 27. How does DNA glycosylase recognize oxidated DNA bases? StarBiochem: human DNA glycosylase (1EBM)
- 38. Structure of human DNA glycosylase structure human DNA glycosylase & DNA function recognition of damaged DNA bases
- 39. Understanding the basis of disease Sickle cell anemia
- 40. Sickle cell anemia severe bone pain and death stroke enlarged heart bloodstream infections and pneumonia www.commercialappeal.com
- 41. A mutation in hemoblogin causes sickle cell anemia University of Utah Learn Genetics website
- 42. Why is hemoglobin sticky in sickle cell anemia patients? StarBiochem: sickle hemoglobin (2HBS)
- 49. Structure of sickle hemoglobin structure mutated amino acid in hemoglobin Disease Val 6 location in hemoglobin makes it sticky
- 54. Thank you! Star Team: Chuck Shubert Ivan Ceraj Rocklyn Clarke Justin Riley Sara Bonner TeamSim Team: Andrew McKinney Kirky DeLong Other Supporters: John Belcher Graham Walker Megan Rokop Kathy Vandiver Phil Bailey Vikay Kumar Peter Wilkins Dr. Lourdes Aleman [email_address] | Molly Ruggles [email_address]
Editor's Notes
- Before you get a chance to explore StarBiochem, I would like to provide a bit of context for why protein structure is worth teaching. We will then move on to use StarBiochem to illustrate some of the central teaching points that this software is perfectly suited for. As Molly previously mentioned, protein structures deal with 3D relationships. Therefore, faculty and teachers face the challenge of communicating and explaining these 3D relationships in traditional classrooms, where 2D mediums are prevalent.
- Why is it that understanding protein structure is an important educational goal in biology classrooms? Proteins are the cells work horses, performing most of the cell’s function. Here are five different proteins that have important functions. Hemoglobin carries oxygen from the lungs to the rest of the body. F1 ATPase produces the energy necessary that allows you to breath, walk, think, etc. Antibodies protect us from current and future infections. Microtubules form the skeleton of the cell and are responsible for properly dividing the DNA content of the cell into two identical halves during cell division. Aquaporins are the proteins that allow the passage of H2O in and out of cells. What is apparent from these examples is that proteins come in many sizes and shapes. Some are globular, others look like long hollow cylinders and others have very unique shapes.
- This diversity in 3D structures has a functional consequence, because the structure of a protein determines its function. In other words, the structure of a protein is directly linked to the specific function that a protein is responsible for. Therefore to understand how a particular protein performs an specific function we turn to its structure.
- StarBiochem allows us to look at protein structures and for all the reasons that Molly previously mentioned, this tool is ideal for educational purposes. Using StarBiochem we can teach our students various concepts, which can be grouped into the following categories. Faculty and teachers can use StarBiochem to learn how the structure of a protein determines its function. In addition, using StarBiochem students can learn how alterations in the structure of a protein caused by mutations can affect how the function of a protein leading to disease. Last but not least the understanding of how the change in the structure of a protein causes disease can lead to the development of smart drugs that act very specifically to inhibit the function of only the altered proteins and nothing else.
- Today we are actually going to do two case studies to illustrate how the understanding of protein structure leads to the understanding of how proteins work and what causes disease and also to give you the opportunity to play with StarBiochem.
- To exploring the relationship between protein structure and function we will turn to DNA repair proteins.
- 10, 000 trillion is the number of DNA mistakes that accumulate per person, per day. This is an extraordinary amount of DNA mistakes that can lead to DNA mutations. 500 are 8oxo Guanine
- If these mistakes are not repaired, they can eventually lead to disease, in particular to the development of cancer. In fact cancer is a complex disease involving the accumulation of mutations in central proteins that control how cells grow and divide.
- I have highlighted several here. DNA mutations can be caused by external agents, such as X-rays, toxic industrial chemical smoking and particular kinds of viruses. In additional DNA mistakes can also be caused by subtances found naturally in the environment such as UV rays, radiation and natural body processes such as breathing and DNA replication.
- Today, we will be exploring a particular kind of mutation called oxidation, which is simply caused by the addition of oxygen radicals and the proteins that help repair this types of mistakes called DNA glycosylases.
- In particular, the question that we will try to answer is how DNA glycosylase recognizes DNA mistakes that are caused by oxidation. To do this let’s no turn to StarBiochem.
- I hope that this small hands-on activity allows you to appreciate how the structure of this protein in its relationship to DNA allows us to visualize how this protein works to recognize damaged DNA bases.
- Now, I will like to turn your attention to the second teaching point that we will be exploring today and for this hands on activity we will be using sickle cell anemia as a case study.
- Sickle cell anemia is a recessive genetically inherited disease of the blood. It has pretty severe symptoms and medical consequences. Patients with sickle cell anemia have severe bone pain. Sickle cell anemia can lead to stroke and other cardiovascular complications such as an enlarged heart and severe infections.
- The reason sickle cell anemia leads to such severe medical problems is because of a mutation in hemoglobin. Hemoglobin is a protein found in red blood cells that is responsible for binding oxygen in the lungs and distributing it throughout the body. In normal red blood cells hemoglobin is freely floating. Normal red blood cells are shaped are compact and flexible allowing them to squeeze through small capillaries. In patients with sickle cell anemia, hemoglobin is sticky and likes to form long, inflexible chains with other hemoglobin molecules. This long inflexible hemoglobin chains, distorted the shape of red blood cells, causing them to become elongated and inflexible. This causes sickle red blood cells to become stuck in small capillaries. This is the reason why patients with this disease often have strokes, enlarged hearts and infections.
- What makes hemoglobin sticky in patients with sickle cell anemia? To understand this issue, we now turn to the structure of sickle hemoglobin in StarBiochem.
- I hope that this small hands-on activity allows you to appreciate how the altered structure sickle hemoglobin, in particular the lysine amino acid at position 6, alters the function of this protein, making it sticky and causing this severe disease.
- To summarize this section of the talk, we can use StarBiochem to teach our students about the relationship between protein structure, their function and disease. We believe that using StarBiochem, students will be able to deepen their understanding of basic biology concepts, while becoming more engaged in the process. Hopefully the usage of StarBiochem also leads to an increase in curiosity and interest in science.
- StarBiochem has been used in both undergraduate and high school settings inside and outside of MIT.