Protein folding

From the reaction coordinate to the energy landscape

A simple chemical reaction often changes only a few bonds. Often stable intermediates can also be isolated, which provide information about the reaction mechanism. The process is usually shown by plotting the Gibbs energy as a function of the reaction coordinate. The classic view of protein folding was also based on this concept of folding paths (pathways) to describe the path of a protein from the unfolded to the folded state. This is also based on results from folding experiments with which certain macroscopic quantities were analyzed.

What makes the analysis considerably more complex and difficult, however, is the fact that in this case an entire macromolecule changes its structure by making or breaking thousands of weak non-covalent interactions. An astronomical number of different conformations must be taken into account. The denatured state in particular is difficult to understand because it represents an ensemble of poorly definable and rapidly fluctuating conformations. Nevertheless, the experimenter is forced to follow the same strategy as would be the case with a simple chemical reaction: to determine the structures and energies of all stable (and metastable) states and transition states as precisely as possible and to determine the kinetics and sequence along the reaction coordinate.

If one now thinks of the individual states (except for the native) not as a well-defined structure (as would be the case with a simple chemical reaction), but rather as an ensemble of many heterogeneous conformations, the accessible conformational space of which, however, is becoming more and more restricted, then you are not that far removed from the image of the energy landscape. In this respect, the curve could represent one (of many) possible paths to get along the funnel wall into the valley. With the concept of the convolution funnel, there is also the fact that the width of the funnel is understood as a measure of the entropy and Q as an additional ordinate, which, however, usually does not run linearly with the Gibbs energy.