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).
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.