Steepest-Descent steps with fixed protein coordinates. This was followed by thermal equilibration in the NVT ensemble for 1 ns, and then 5 ns of molecular dynamics under isothermal-isobaric (NPT) conditions, with the protein backbone constrained by applying harmonic constraints with a 10 kJ mol -1 Å -2 force constant to the CA atoms. Structural restrictions were then lifted, and 1 ns simulations were conducted under constant pressure and temperature, followed by production simulations for 10 ns also in the NPT ensemble. To ensure adequate sampling of the solvent, 20 independent simulations were performed for each system . We opted for multiple production simulations of 10 ns because the purpose of the study is to understand the solvation of the native state of Ubiquitin in various solvents.