Protein melting: the Lindemann criterion applied to proteins

The full knowledge of the structural and dynamic properties of the native, transition, intermediate, and denatured states of proteins is a key goal of life and physical sciences. Indeed, this kind of information can lay the foundation for the deep understanding of folding and unfolding of proteins which, in turn, are crucial processes in the metabolism of cells, regulating biological activity and targeting proteins to different cellular locations. In our work (Katava et. al., PNAS (2017) here)we focus the attention on the sub-nanosecond dynamics of a model protein in correspondence of the melting transition, when it is embedded in three different solvents. We show that, although the different solvents modify the protein melting temperature, a common scaling toward a constant value for the local fluctuations is attained when approaching the unfolding temperature.
Quite remarkably, this result is reminiscent of the famous criterion for melting of solids proposed by F.A. Lindemann in 1910, which states that crystals liquefy when their atomic root mean square fluctuations exceed a certain threshold value. The common scaling we found for protein mean square displacements at melting not only sheds unique light on the relationship between protein flexibility and stability, but also opens the possibility to predict protein unfolding in special environments (e.g., the cell interior) by following thermal local fluctuations.
The striking analogy between the melting of inorganic crystals and native biomolecules suggests that these seemingly very different systems may share similar behavior in correspondence of phase transitions. On these grounds, we may speculate that simplified theories of solids can also be effectively applied to interpret the behavior of complex biological systems.