European Commission logo
English English
CORDIS - EU research results
Content archived on 2024-05-27

The protein thermostability: same activity, different working temperature. A water problem? A rigidity/flexibility trade-off?

Final Report Summary - THERMOS (The protein thermostability: same activity, different working temperature. A water problem? A rigidity/flexibility trade-off?)

In nature some organisms thrive in very extreme environments. In particular, thermophilic organisms optimally grow at temperatures as high as the boiling point of water. In this project we have investigated how the molecular machinery of these organisms, namely their proteins, sustain life in these extreme conditions. In our project we have deployed a series of computational methods for deciphering the molecular factors that grant the enhanced stability of the thermophilic enzymes. We showed for instance that the presence of internal water in the core of the proteins ensure extra cohesive forces making the protein resistant to temperature. In other words, water act as internal glue. Enzymes can therefore be engineered by creating wet cavities. We have also probed that not necessary the protein matrix rigidity correlates to the stability at high T, and that, as for earthquake resistant buildings, flexibility can ensure this thermal resistance. Of course, as we have pointed out in several investigations, talking about flexibility/rigidity in general is too vague. In fact it is necessary to specify which modes are involved in functionality and in unfolding paths. Again, in protein design this knowledge will help plug flexibility without corrupting functionality. The ensemble of analysis we have proposed and based on network representation of protein conformational states, can be useful for this purpose. Finally, it has to be considered that, in vivo, the stability of proteins is conditioned by the highly crowded cellular environment. Because of the size- and the time-scales of the problem a simplified representation of the molecular system is needed. Our methodological development for multi-scale simulations of proteins in a fluid is capable of addressing this issue and is very promising for future applications.
In conclusion, our investigation helped to clarify some molecular aspects of the stability/functionality trade-off in proteins by using thermophilic enzymes as model. Moreover, it has produced a very innovative simulation scheme to approach the proble of protein mobility and stability in vivo like condition. Finally, it has offered the possibility to our group to create inter- and cross-disciplinary collaborations that will be active well beyond the conclusion of the project.