Exercise planning Put only TWO numbers on each genome--one for your first child; one for you second Make it clear we’re staying with RNA genome; no changes to T Fully disperse the group before having them go to ‘shuffled’ positions

2 Anfinsen A1) each molecule more or less instantly goes to fully correct form. It’s a ‘snowball rolling down hill’ model, where each correct association greatly enhances the subsequent. So my 2nd bond is quicker than your 1st. Predicts precise tracking of disulfides formed vs. achieved activity

3 Anfinsen A1 A1) each molecule more or less instantly goes to fully correct form. It’s a ‘snowball rolling down hill’ model, where each correct association greatly enhances the subsequent. So my 2nd bond is quicker than your 1st. Predicts precise tracking of disulfides formed vs. achieved activity

4 Anfinsen A2 A2) Only correct bonds form, but with different rates for different bonds--so there is an order and timing of bond formation that is the same for all molecules. So A-A’ might form quickly; B-B’ slowly, etc.

5 Deadline = line + dead deadline | ˈ ded ˌ līn| noun 1 this definition not relevant 2 historical a line drawn around a prison beyond which prisoners were liable to be shot. think about it Does it really make sense to designate that period at the end as the target as opposed to that at the beginning? Is it really the case that your schedule is such that all available times just happen to fall at the last minute?

6 Beating Tamiflu Themes: Evolution: then and now amino acids, mutations, folding: they matter Themes: Evolution: then and now amino acids, mutations, folding: they matter

7 How evolution happens Good ideas are rewarded not sought/planned There’s no mechanism for foresight, so it cannot be that way

8 How the flu happens

9 Just passin’ through

10 Just passin’ through

11 Just passin’ through

12 Midterm There will be one Periodic Table, Hemoglobin, DNA, proteins, Anfinsen Study TOPIC guide will appear Oct. 18

13 Tamiflu: you shall not pass! a.k.a. oseltamivir

14 And it goes like this... Note: this is modeled, not a crystal structure

15 Fluorescence Scorpion glows in the dark!

16 Cell sorting Laser is like a black light-- molecules GLOW a different color than they are being hit with In our case, GFP (green) and cherry (you guess)

17 GFP: paint by numbers Tsien lab GFPs! “Inward-facing sidechains of the barrel induce specific cyclization reactions in the tripeptide Ser65–Tyr66–Gly67 that induce ionization of HBI to the phenolate form and chromophore formation. This process of post-translational modification is referred to as maturation.[22] The hydrogen-bonding network and electron- stacking interactions with these sidechains influence the color, intensity and photostability of GFP and its numerous derivatives.”chromophore Not the words, but the sense --Wikipedia, “GFP” *

18 Shadowboxing

19 What you’ll see ‘illuminated’ from left shows how much green ‘illuminated’ from below shows how much red

20 Vocab & Paper This is a challenge--and I’m not ashamed of that Challenges require a combination of EFFORT and THINKING

21 Phylogenetic trees Participants: to your spot on the tape! Observers: watch & predict outcome and what it’s good for Each round: Copy any changes your parent already has Determine position of your new change by adding #s (0 = none) Randomly change to new base & mark (A, G, C, U) Turn to your kids & repeat

22 Derived rules Better ‘trees’ = trees with the fewest total changes from neighbor to neighbor We can infer missing ancestors by comparing the kids Older mutations appear in more of the children (and all of the children derived from the initiator

23 Which makes sense? Or this?

24 Supplemental Stuff you might find useful

25 Supplemental Cartoon of infections & tamiflu action (contr. Katie F12)

26

27 Now what??? What information allows you to make good inferences about who is most related? Who gave rise to whom?

28 How about this?