Hyperthermophilies and thermophilies are organisms that grow at temperature higher than normal ambient condition. The former thrive optimally between 80° and
100° C while the latter between 50° and 70°. Their molecular machinery is then suited to function at extreme temperatures. Enzymes from these organisms generally do not work at temperature below 40°, that is the optimal working condition for enzymes from mesophiles. Until now the microscopic origin of thermostability of enzymes from (hyper)-thermophilic organism remains unclear. We use computational methods to study how hyperthermophilic proteins resist to thermal stress. In particular we are interested in understanding
- Role of hydration on protein stability
- The specificity of the conformational landscape of thermostable proteins under different thermodynamic conditions
- The effect of temperature on the enzymatic activity of thermophiles
- The correlation between thermal and mechanical resistance
We use a multi-method & multi-scale approach for sampling and investigating the protein behavior at different time and length scales.
This line of research is funded by the European Research Council via the ERC Starting-Grant programme IDEAS (proposal 258748-THERMOS).
This research is made is collaboration with S. Melchionna at CNR, Rome IT. The collaboration with D. Madern of the Extremophilic and Large Molecular Assemblies Team, IBS, Grenoble, specifically focus on the stability of multi-domain proteins.
In order to track the behaviour of proteins and investigate their functionality adequate computational schemes, suitable to cope the broad range of characteristic time- and lenght-scales of biosystems, must be adopted. We develop and apply method coupling coarse-grained model for proteins with hydrodynamic interactions, enhanced sampling methods as well as mixed quanto-classical methods.