Molecular dynamics simulation studies of rubredoxin from Desulfovibrio gigas (RDG) were used to characterize the molecular mechanism of thermal stabilization by the compatible solute diglycerol-phospate (DGP). DGP is a negatively charged compatible solute that accumulates under salt stress in Archaeoglobus fulgidus. Experimental results show that a 100mM DGP solution exerts a strong protection effect in the half-life of RDG at 363 K1. RDG was simulated in four aqueous solutions at   300 K and 363 K: pure aqueous media, 100mM DGP, 100mM NaCl and, 500 mM DGP. Our work shows that the 100mM DGP solution is able to maintain the average protein structure when the temperature is increased, preventing the occurrence of large scale deviation of a mobile loop involved in the first steps of RDG unfolding. The molecular mechanism of thermal denaturation protection by DGP seems to involve the direct interaction between the protein and the compatible solute by hydrogen bond interactions near the mobile loop. Several clusters of DGP molecules are formed and preferentially localized at neutral electrostatic regions of the surface. The increase of DGP concentration to 500mM did not yield better stabilization of the protein suggesting that the thermal protective role of this charged compatible solute is achieved at low concentrations, as shown experimentally.