Based on lecture 2, we now expand the free energy concept and separate it into Helmholz vs. Gibbs free energies. This is an important formal definition difference, since the latter introduces the constant pressure we typically have in the lab. However, for proteins this difference is typically negligible since we deal with extremely low concentrations - so for the rest of the course we will typically just talk about "free energy", we will use the letters (G) corresponding to the Gibbs one, but because of the small difference we never bother about pressure.

We will show you how the temperature actually comes out as a natural definition from the F=E-TS equation, and this is the proper thermodynamic definition of temperature. We then go back and revisit the hydrophobic effect, but now we can describe it properly with the free energy nomenclature, and also start relating it to protein folding.

We talk about the strength of electrostatics, why water has a very high value of epsilon (due to screening), and that proteins have a much lower epsilon - which will make the electrostatics interactions much stronger in them. Finally, all this is related to the titratable amino acids, and we observe that it's quite common for them to be neutral (adding or losing a proton to water) if we force them to the inside of proteins.

Reading instructions

Chapters 5 & 6 in the book

Study questions

What is the difference between Helmholz & Gibbs free energy? (in theory & practice)
Give some examples of (a) relevant and (b) irrelevant energy barriers at 300K!
How can you predict what processes will occur?
Have a look at http://bit.ly/1o5f1jP for detailed derivation!
What is the difference between h-bonding in vacuo and water?
What are partition coefficients?
Why are free energies so intimately coupled to experiments?
What is the definition of temperature?
How does the hydrophobic effect vary with temperature? Why?
Why is hydrophobic ΔG so well correlated with nonpolar area?
What is the role of ε? Why is the water value so extreme?
Why does ε go down for high-frequency electric fields?
What is ε roughly inside a protein?
What does the book mean by “electrostatics in water originates not from energy, but from entropy”?
What usually happens to titratable amino acids inside proteins?

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