The origin of pressure resistance in deep-sea lactate dehydrogenase

The deep ocean presents an interesting paradox since it is teeming with life despite the high-pressure environment. This is due to evolutionary adaptations in deep-sea organisms, such as amino acid substitutions in their proteins, which aid in resisting the denaturing effects of pressure.

However, the physico-chemical mechanism by which these substitutions can induce pressure resistance remains unknown. Here, we use molecular dynamics simulations to study pressure-adapted lactate dehydrogenase from the deep-sea abyssal grenadier (C. armatus), in comparison with that of the shallow-water Atlantic cod (G. morhua). Alchemical thermodynamic integration and the Archimedean Displacement Method were used to determine whether pressure resistance is due to a thermodynamic stabilization of the native state of the protein or to an increase in the volume of the denatured state.