World's Fair

The laws of thermodynamics are empirical laws – they were not derived from some first principles of the universe: they were derived by doing thousands and thousands of experiments, and then coming up with some relationships that could quantitatively explain all those experiments.

In biological thermodynamics, we are at the beginnings of trying to define a similar set of “laws of biothermodynamics” – in this case we want relationships that connect thermodynamic quantities (ΔG, ΔH, ΔS, ΔCp) to functional or structural information about the biomolecules themselves. Nobody has anything that could actually be called a “law” yet, but there are some very interesting “guidelines”, and one of the strongest of them is about heat capacity (ΔCp).

It turns out that ΔCp is quite strongly related to the change in exposed surface area during a biological reaction. In other words: if two proteins interact and bury some surface area in an interaction interface – you’ll see a big heat capacity change (a big ΔCp). When a protein folds from a random coil into the nice structures you see in textbooks, again it buries a lot of surface area that was exposed in the random coil and now is tucked inside the folded protein – and again: a big heat capacity change is observed. But here is the exciting part: the measured ΔCp for many types of biological reactions is directly quantitatively proportional to the amount of surface area that gets buried or exposed.

This means that if you are studying two proteins that associate to form a dimer, and you measure the ΔCp of dimer formation, you can then often directly calculate the area (usually in square angstroms) of the interaction interface between the two proteins. No crystal structure involved – you are getting highly precise structural information (size of the protein-protein interface in square angstroms) directly from measuring a thermodynamic quantity (ΔCp).

i-972a3a14b4f8d81ce072e30967abb856-Heat capacity proteins.jpg

And, as noted in the figure, the sign of the heat capacity change also provides information: a negative ΔCp indicates burial of surface area while a positive ΔCp indicates exposure of surface area (i.e. if the reactions in the figure go in the opposite direction, they will have positive ΔCp values). [Note: this explanation is a bit of an oversimplification of the exact quantitative relationships between surface area changes and heat capacity, but the general relationships are correct.]

And the reason this all works is similar to the reason the laws of thermodynamics work: many, many labs have measured both sides of the equation (the heat capacity side and the area of interaction side) and found that the correlation works virtually all the time – for some types of biological reactions – it works virtually all of the time for protein folding and protein-protein interactions, it only works about half of the time for protein-DNA interactions. It’s still very much an area of active research, since the feeling is: it works so well for so many biological reactions, maybe there are just a few more aspects of the correlation we need to discover to get to where it would be a “law of biothermodynamics”.

The next installment of “Heat Capacity in Biology 101” will describe how you detect and measure a ΔCp for a biological molecular reaction.


  1. #1 sascha vongehr
    September 24, 2010

    “The laws of thermodynamics are empirical laws – they were not derived from some first principles of the universe”

    Are you joking? That they have been historically discovered this way does surely not mean you can just disregard the firm foundation of statistical mechanics that thermodynamics is nowadays resting upon. Moreover, that the degrees of freedom go down when dof become coupled at a common surface and that thus, in most cases, the heat capacity will go down accordingly, is well expected from statistical mechanics. Surely, you know this, so why do you write here as if it is all some thermodynamic mystery?

  2. #2 Richie
    October 30, 2010

    I agree with the laws of thermodynamics as tested in the lab however how do you calculate man made carbon dioxide when 72% of the planet is under oceans and nobody has the slightest clue how many undersea volcanoes that are active? There could be 300% or more unknown CO2 spewing sources under our oceans. When the main greenhouse gas, water is 99.9 % more prevalent than Carbon dioxide why has the climate never run away as you all claim a couple parts per million of CO2 is supposed to do. What happened to the 4500 missing weather stations that we used up until 1970s. How do you compare the temperature of a planet over time when you are not even using the same data sources? Why are 300 weather stations in Canada’s Arctic ignored and only one used? It’s situated on an Island known as the garden spot of the Arctic.

    There is massive uncertainty in global warming theory that will be better explained in AR5 instead of hidden in AR4.

    The laws of thermodynamics as tested in the lab are very different from the real world!

  3. #3 Thomas
    Hong Kong
    November 24, 2013


    Send me the references that supports your argument that surface area in foldng proteins contradicts classical thermodynamics. Specifically, in what way is there a contradiction.

    • #4 Vince LiCata
      January 30, 2014

      Hi Thomas,

      I don’t believe I say that any of this contradicts classical thermo – I mean, it doesn’t. We just don’t know exactly what all the contributions are
      at the molecular level that produce the measured thermodynamics yet. I do say that the correlation between surface area and heat capacity doesn’t hold
      in all biological reactions – that’s just an empirical finding and just means we don’t fully understand their connections, it definitely doesn’t mean any thermo is being violated.

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