We start this lecture with a few examples of how you already now can use free energy to draw some pretty deep conclusions about nature and what is possible - or not. Do read the polywater material below, and become a better scientist while you're at it!

After the physics detour we now go back to proteins and the simple polypeptide chains. We talk about enthalpy vs. entropy in energy landscapes, and then study secondary structure in terms of free energy. The repeat of the alpha helix is on the one hand obvious, but on the other quite subtle since the shape gives the helix some of its most important properties in proteins. We study hydrogen bonds in particular, and what it means in the Ramachandran diagram. Beta sheets have different properties, but here too the key is how they give proteins specific functions. We look at a few different ways to determine secondary structure, and compare them conceptually.

In this lecture we also look more into specific amino acids such as Proline & Glycine - what do their properties mean e.g. for entropy? Now we also discuss the disulphide bridges of Cysteine, and how Tryptophan is big & bulky - which incidentally is a key feature of the world's smallest protein Trp-Cage. It turns out the charged amino acids are also critical for stabilizing and strengthening effects of the alpha helices, and the geometry of alpha helices and beta sheets can give them a "hydrophobic moment".

Finally, we talk more about the titratable amino acids and the concept of "pKa value", and why the charges can be exceptionally important for function.

Reading instructions

Book chapters 7 & 10

What are the fundamental differences between helices and sheets in term of stabilization properties? How do you think they form?

Study questions

How are energy landscape properties related to energy / entropy?
What is the hydrogen bond pattern in the most common helix?
What free energy components do you think (a) favor (b) disfavor helix folding?
What free energy components do you think (a) favor (b) disfavor sheet folding?
What is the historical way to get secondary structure? What would you do?
Why do you gain so much energy from solvating D/E/K/R?
What is a disulphide bridge? What is their role?
Tryptophan has many special properties, but one useful biophysically. What?
Why do you get a helix dipole?
What is helix capping?
Why is the right-handed alpha helix by far the most stable helix?
Why are beta sheets twisted?
Explain the difference between states and microstates!
Based on the labs, how would you explain multiplicity relative to microstates?
Based on what you now know, how would you explain entropy?

Videos

Folding of the Trp Cage mini-protein in a computer simulation

Slides

Handout-format slides for lecture 4

Full-format slides for lecture 4

Scientific papers and other material

The curious case of polywater

Debunking polywater