Strings to Blobs

1. (chains of amino acids -> folded proteins) Strings to Blobs Hemoglobin

2. What Matters Today? • Protein = biological machine • How do you build a machine that builds a machine, that builds a machine, that (etc.)? • Machine = 3D object that does stuff = protein • How do we get the shape (the fold) of the protein?

3. Review: bonds • A few pieces of review

4. Four ‘bonds’ • Covalent: like a dowel. Arises from? • Ionic: like a rare earth magnet. Arises from? • Hydrogen: like a wimpy old fridge magnet. Arises from? • Hydrophobic: like nothing else. Arises from?

5. “Building Blocks” • There are ~ 4 ways molecular surfaces can ‘feel’ • What are they? • Go to the Control Center -> Resources -> All aa surfaces (aa = amino acid)

6. Amino Acid Information

7. Which amino acid do you have? • Pairs receive amino acid models • Pairs identify their amino acid • Control Center -> resources -> amino acid -> codes and abbreviations

9. What does YOUR amino acid feel like? • Be ready to stand up and tell the class • Base your answer on electronegativity values • O > N > C = H - Can also look in: control center -> resources -> amino acid -> surfaces to verify

10. Other aspects of YOUR Amino Acid • How long is it? • How flexible? • How bulky? • Any other odd things you notice about your amino acid?

11. Inside and Outside • Protein folding, oil/water, membrane formation all same principle • Protein folding- individual units attached to a pair of neighbors • Many proteins need no further ‘instruction’ than sequence & water

12. How does protein ‘folding’ happen? http://amit1b.files.wordpress.com/2008/03/protein-folding2.png

13. Why oil and water don’t mix (hydrophobic effect) http://blc.arizona.edu/courses/mcb184/MiniLects/Phobicity08.mov

14. Boring (uncharged/greasy) clumped together

15. Where the analogy breaks down • At a party, the action is directed – people purposely move away from the boring people • In an oil and water mixture it is all chance – molecules move randomly (Brownian motion), eventually resulting in hydrophilic and hydrophobic molecules being together in separate groups

16. More important points • It is water’s NON-AFFINITY for the oil that brings about oil molecules being together • Oil (or other non-charged molecules) has/have no affinity for itself • Hydrophobic bonds or interactions are not active ‘bonds’ in that there is no actual interaction between the hydrophobic molecules

17. One more time Purple = water molecules Yellow = oil (non-charged) molecules

18. Minimize oil’s interaction with water, water has more opportunity to interact with itself Purple = water molecules Yellow = oil (non-charged) molecules

19. If THIS is true… • Pencils made of…. http://www.nano-enhanced-wholesale-technologies.com/faq/carbon-forms.htm

20. If THIS is true… • Pencils made of…. • Paper made of…

21. If THIS is true… • Pencils made of…. • Paper made of… • Oil and water… • Pencils, paper, oil, water…

22. Your Turn • You ‘fold’ a protein: ProFolder(Control Center -> Non-assessor Software -> not for credit and other software ) • Open ProFolder, click ‘Navigation’ • Select ‘folding’, then ‘pre-set challenges’ • Show me each solution • Leave 2nd solution on screen

23. Profolder Features • SYMBOLS – look at these before you start • Navigation (lower right) => Folding • Top: amino acid string • Squares: places amino acids could go. Note ‘Undo last’ button • Two spots--use one to improve upon what you did in the other • Bottom: note that when you mouseOver an amino acid, it’s structure & ‘feel’ are shown

24. How does yours compare?

25. Primary: http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology

26. You’ve seen this before: Amino Acid sequence Secondary: Alpha Helix How is this determined? http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology

27. How do hydrogen interactions (H-bonds) contribute to alpha-helix and beta-sheet?

28. (+) (-) Other ‘rules’ of folding

29. Picture of alpha-helix and beta-sheet http://www.ebi.ac.uk/training/online/course/biomacromolecular-structures-introduction-ebi-reso/proteins/levels-protein-structure

30. You’ve seen this before: Amino Acid sequence Alpha Helix Folded peptide Tertiary: http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology

31. You’ve seen this before: Amino Acid sequence Alpha Helix Folded peptide Aggregation of peptides http://compbio.pbworks.com/w/page/16252897/Introduction-and-Basic-Molecular-Biology

32. Now let’s “Hemoglobin” • Hemoglobin = Hb

33. There are ~280 MILLION Hemoglobin Molecules Per Red Blood Cell Where we are: Hb made of four protein chains ‘subunits’ Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease

34. Staying Zoomed In

35. Where we are Oxygen IS molecular, so TWO oxygen atoms Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease

36. Hb made of four Protein chains 2 alpha chains 2 beta chains

37. Hemoglobin

38. Hemoglobin

39. Hemoglobin • How hemoglobin’s amino acid sequence promotes its function

40. Hemoglobin • How hemoglobin’s amino acid sequence promotes its function • Whyhemoglobin is a tetramer (gang of four)

41. Running the Tutorial • Control Center -> In-Lab activities • Group name = first three letters of your first names (WRITE THIS DOWN IN YOUR LAB NOTEBOOK) • READ the instructions on the intro... • READ the instructions on each question... • READ the instructions on the webpage... • READ all the words of each question...

42. Do it with ‘feeling’

43. READ QUESTION 13 CAREFULLY!!!!!!!!! • What do you need from me in order to proceed?

44. Understanding the Model

45. What is different?

46. What is different?

47. What does that correspond to on the ‘butterfly’ model?

48. What’s wrong with this model?

49. All the slides about how the model(s) sucks and how the ‘butterfly’ model matches up to actual hemoglobin can be talked about using these slides with your whole class, or can be talked about with individual small groups or a combination of both

50. Homework– see Control Center