Unfolding is a crack!

The atomic force microscopy and other single molecule techniques have inspired a body of theoretical work aimed to detail the unfolding process of proteins.

A related intriguing question is: at which extent the unfolding due to a perturbative external mechanical force overlaps with the temperature (or chemically) induced process? There is not reason to think the two processes to be identical, and in principle a thermostable protein could lacks resistance along the pulling direction. However, it is tempting to follow the unfolding mechanism in different cases (temperature, chemical, and force induced) and see whether or not they can be mapped onto a similar problem-class.

I cite here a very interesting work by de Graff, Shannon, Farrel, Williams and Thorpe appeared in Biophysical Journal in 2011, see the pdf here. They used a simplified, but realistic enough, model to describe force induced unfolding of a protein as the crack propagation in a network. The model describes the protein matrix as a network of interactions between rigid units, and these interactions can break as effect of the applied external force mimicking the pulling of the protein's terminals. The progress of the cracking is followed and successfully compared to the unfolding processes caused by external force and generated by molecular dynamics simulations at the atomistic resolution. The great advantage of the model introduced by Thorpe and coworker is the computational cost, quite low as compared to the cpu-time required to perform atomistic simulations. The dissolution of a connected rigid network induced by progressively scaled interactions has been previously used to model thermal denaturation. In particular some investigations were devoted to thermophilic proteins and their thermal stability, see Rader, PhysBio(2009) and Rodestock&Gohlke, Protein(2010). The authors showed that in the matrix of thermophilic proteins the dissolution process of the network is more difficult to occur as effect of a more robust connectivity of the rigid motifs. The idea to compare temperature and force unfolding path echoes also in other recent papers, more or less innovative, see Srivastava&Granek, PhysRevLett(2013) and Prasanth&Andricioaei, NatureComm(2012).

Unfolding pathway of barnase protein. de Graff et al, Biophy J (2011),  101, 736.