Tracking the corresponding state principle

Maria KALIMERI just graduated from Univ Paris VII. Congratulations! Her thesis focused on mechanical properties of thermophilic proteins explored via an innovative framework based on network analysis. Here a bite of her work "Understanding the relation between protein flexibility, stability and function remains one of the most challenging, open questions in biophysical chemistry. For example, proteins need to be flexible to facilitate substrate binding but locally rigid to sustain substrate specificity. Exemplary cases are enzymes from microorganisms that thrive at elevated temperatures, also referred to as thermophiles. These proteins are stable and functional at the high temperature regime but generally lack activity at ambient conditions. Therefore, their thermal stability has been correlated to enhanced mechanical rigidity through the corresponding states paradigm. The generality of this view, however, has been questioned by a number of

experimental and computational studies. In the present study, we employ the gold standard of computational techniques, namely Molecular Dynamics simulations, in order to identify microscopical characteristics that distinguish thermophilic from mesophilic proteins, elaborating in particular on the rigidity paradigm mentioned above." For a more complete reading see here.

Yellowstone Thermophiles

Beautiful pictures. I found an interesting web-site dedicated to thermophilic life in the Yellowstone National Park (US), see here. I quote from the home page "There is so much to know and so much to find out about the extreamophiles in Yellowstone National Park. Since the discovery of Thermus aquaticus in 1969 a universe of interest has surrounded the life forms that survive - even thrive at very high temperatures. At the time that Thomas C. Brock and Hudson Freeze reported the new life form, it was thought that only a few organisms could survive at high temperatures above about 130F. Since its discovery, interest has spread and much has been learned. The scientific community has devoured the subject with relish. Only recently has this knowledge crept into the popular mind. As people learn of the extreme conditions of life at 175F they want to know more. It's fascinating and awe inspiring. It is a concept that is wondrous to contemplate. Questions are asked: "What do they eat?" - "How big are they?" - "Where are they?" - "How do they do it?" - "What do they look like?" The answers are as fascinating as the organisms. I would like to help answer the last question above. As I travel in Yellowstone I am drawn to their colors and patterns and diverse images that they etch on my eye. I take some snapshots and present a few of them here." Enjoy the Gallery!

Antifreeze protein with a heart of ice

The four helical bundle of the large antifreeze protein Maxi is glued in one, not primarily by protein-protein interactions but via an extended network of water pentagons! See picture below. The protein was recently crystalized by Peter Davies and his group and published in Science, 2014. 

This finding points to an important open question: What is the contribution of internal water to the stability gap between different homologous proteins (psychrophilic, mesophilic and thermophilic)?

A physical mechanism behind thermal stability

A little less than a decade ago a study suggested that there are two major physical mechanisms for protein thermal stabilization depending on the evolutionary history of the source organism, a ''structure-based" and a ''sequence-based" one [Berezovsky and Shakhnovich, 2005]. Proteins from organisms that originated in hot environments (therein archaea) have a much more compact structure and hydrophobic core. On the other hand, proteins from organisms that started as mesophiles and later recolonized a hotter environment (therein bacteria) remain structurally similar to mesophilic homologues but present some sequence substitutions that result in a few key interactions in the final fold. 

However, this strict assignment of evolutionary history to these two domains of life, archaea and bacteria, has no solid ground. In fact, more recent studies showed that the ancestors of bacteria were also thermophiles [Boussau et al., 2008; Akanuma et al. 2013]. Yet, the same study had also another dark point. The structure of the hyperthermophilic protein rubredoxin from archaeon Pyrococcus furiosus was found to be more tightly packed (number of contacts per residue) as compared to the rubredoxins from another 3 mesophilic bacteria. This result seems to contradict an earlier H/D experiment suggesting that the flexibility of this protein is typical to that of mesophiles [Hernandez et al., 2000] but the authors dedicate no comment to that. One certain aspect is that structural studies, although they put things in a first informative perspective, they neglect dynamics and are based on X-ray structures resolved at low temperatures. Notably, the effect of temperature on the structure and the magnitude of fluctuations of the exact same protein has been pointed out by short timescale MD simulations [Ergenekan et al., 2005]. Although the dynamics of rubredoxin from Pyrococcus furiosus was quite recently studied in detail using incoherent quasi-elastic neutron scattering in combination with MD [Borreguero et al., 2011], further comparative MD studies between mesophilic and thermophilic rubredoxins might shed light to contradictions such as the above.