The project is meant to describe the complexity of cold adaptation in psychorphilic enzymes, by investigating their catalytic properties and comparing them to their homologous mesophilic or thermophilic counterparts.
So far, a number of such comparisons [1,2,3] have provided evidence, that the temperature adaptation is mainly dictated by a trade-off between protein flexibility, crucial at low temperatures, and protein stability, essential to withstand thermal denaturation . Our aim will be to add new similar studies and further explore the impact of surface flexibility (softness) on catalytic rates, particularly the means of its influence on the active site of the enzymes, which is usually rigid and conserved between homologous enzymes[5,6]. The hypothesis relating surface softness to more negative entropic (TdS) contribution towards transition state free energies in cold adapted enzymes will also be thoroughly tested.
The main methods employed to this task would include MM/EVB and QM/DFT, as well as production of longer MD trajectories in order to analyze and compare the mobility of certain regions in homologous enzymes. Here, the accurate DFT calculations of specific reference states would be of utmost importance, serving as a validation of proposed catalytic mechanisms, in case where these are ambiguous, but also providing accurate free energy values that are crucial input to EVB approach.
 Bjelic, S.; Brandsdal, B. O.; Aqvist, J. Biochemistry 2008, 47, 10049–10057.
 Isaksen, G. V.; Åqvist, J.; Brandsdal, B. O. PLoS Comput. Biol. 2014, 10 (8), e1003813.
 Åqvist, J. Biochemistry 2017, acs.biochem.7b00523.
 Åqvist, J.; Isaksen, G. V.; Brandsdal, B. O. Nat. Rev. Chem. 2017, 1, 51.
 Siddiqui, K. S.; Cavicchioli, R. Annu. Rev. Biochem 2006, 75, 403–433.
 Papaleo, E.; Riccardi, L.; Villa, C.; Fantucci, P.; De Gioia, L. Biochim. Biophys. Acta - Proteins Proteomics 2006, 1764 (8), 1397–1406.
We have published an article (Socan, J., Kazemi, M., Isaksen, G. V., Brandsdal, B. O. & Åqvist, J. (2018). Catalytic Adaptation of Psychrophilic Elastase. Biochemistry, 57(20), (2984-2993) using some of its computational resources from this project.