CONICET | Buscador de Institutos y Recursos Humanos

Cold denaturation of globular proteins is an intriguing phenomenon that deserves special attention. Thus, the hydrophobic effect is considered the main driving force for folding and protein stability, as well as the loss of the protein stability when its upon cooling. Experimental and theoretical evidence recognize the role played by the density of water and its temperature-dependence that are largely determined by the energetic and geometric features of H-bonds. Hence, there are those who argue that the model proposed by Frank and Evans in 1945 confirm that the H-bonds in the hydration shell of non-polar solutes are stronger and ordered thanthose in bulk water in the cold denaturation. However, the Muller's model and some experimental data indicate that the hydration shell is more disordered or more broken, than those in bulk water. Therefore, there is a discrepancy in the microscopical model for the cold denaturation. With the intention of understanding this phenomenon, we have chosen as alternative approach Molecular Dynamics simulations (MD) using the Gromacs-2018 package and analyzing the cold denaturation of the Yfh1 frataxin of S. cerevisiae. In this study, we created two system at 225 K and 1 bar. For the first system the protein was immersed into the box with water with a solid seed of Ice Ih in solid state. Meanwhile, the secondsystem was hydrated by adding water molecules randomly in liquid state. After 1μs of simulation trajectories the first system was crystallized in Ice Ih (freezing), hwhile the second system (without seed) remained in liquid state. Our MD simulations shows details of in the number of number of hydration shell H-bonds and the reorganization of water-water and water-proteins H-bonds during to cooling, showing a decrease in water density due to an increased in the fraction of the water molecules with a perfect tetrahedral coordination modify the solvent accessible surface area in the protein in dependence with hydrophobic effect.