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

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Strings to Blobs


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what matters today
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?
review bonds
Review: bonds
  • A few pieces of review
four bonds
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?
building blocks
“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)
which amino acid do you have
Which amino acid do you have?
  • Pairs receive amino acid models
  • Pairs identify their amino acid
    • Control Center -> resources -> amino acid -> codes and abbreviations
what does your amino acid feel like
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

other aspects of your amino acid
Other aspects of YOUR Amino Acid
  • How long is it?
  • How flexible?
  • How bulky?
  • Any other odd things you notice about your amino acid?
inside and outside
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
how does protein folding happen
How does protein ‘folding’ happen?

http://amit1b.files.wordpress.com/2008/03/protein-folding2.png

why oil and water don t mix hydrophobic effect
Why oil and water don’t mix (hydrophobic effect)

http://blc.arizona.edu/courses/mcb184/MiniLects/Phobicity08.mov

where the analogy breaks down
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
more important points
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
one more time
One more time

Purple = water molecules

Yellow = oil (non-charged) molecules

minimize oil s interaction with water water has more opportunity to interact with itself
Minimize oil’s interaction with water, water has more opportunity to interact with itself

Purple = water molecules

Yellow = oil (non-charged) molecules

if this is true
If THIS is true…
  • Pencils made of….

http://www.nano-enhanced-wholesale-technologies.com/faq/carbon-forms.htm

if this is true1
If THIS is true…
  • Pencils made of….
  • Paper made of…
if this is true2
If THIS is true…
  • Pencils made of….
  • Paper made of…
  • Oil and water…
  • Pencils, paper, oil, water…
your turn
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
profolder features
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
slide25

Primary:

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

slide26

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

picture of alpha helix and beta sheet
Picture of alpha-helix and beta-sheet

http://www.ebi.ac.uk/training/online/course/biomacromolecular-structures-introduction-ebi-reso/proteins/levels-protein-structure

slide30

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

slide31

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

where we are

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

where we are1
Where we are

Oxygen IS molecular, so

TWO oxygen atoms

Image source: http://www.myoptumhealth.com/portal/ADAM/item/Sickle+cell+disease

slide36

Hb made of four

Protein chains

2 alpha chains

2 beta chains

hemoglobin2
Hemoglobin
  • How hemoglobin’s amino acid sequence promotes its function
hemoglobin3
Hemoglobin
  • How hemoglobin’s amino acid sequence promotes its function
  • Whyhemoglobin is a tetramer (gang of four)
running the tutorial
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...
read question 13 carefully
READ QUESTION 13 CAREFULLY!!!!!!!!!
  • What do you need from me in order to proceed?
slide49

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