High pressure environments are prevalent in our universe, ranging from the relatively modest pressure of the deep ocean to the extreme high pressure of planetary cores. Unlike temperature, which accelerates all elementary reactions regardless of their mechanism, increases in pressure will favour only those reactions that yield a decrease in the volume of the system, according to the fundamental thermodynamic relationship: \(\Delta V = \left(\frac{\partial \Delta G}{\partial p}\right)_T\). Application of pressure can therefore induce some very interesting and unexpected chemical and physical transformations. Pressures on the order of 1 kbar will result in the unfolding of most proteins, due to the loss of internal cavities and hydration of previously buried amino acid residues in the unfolded state.[1] Extreme high pressures can result in surprising changes in the electronic properties of materials, such as the transformation of sodium to a transparent insulating material at 2 Mbar[2] and the recent discovery of solid metallic hydrogen at 4.25 Mbar.[3]

Unfortunately, extreme high pressure conditions are difficult and expensive to generate in a laboratory setting. Molecular dynamics simulations provide an attractive alternative for studying processes at high pressure. In this talk, I will review our recent work on the kinetic isotope effect in metallic hydrogen using path integral molecular dynamics, and our investigation into the physico-chemical mechanism of pressure resistance in proteins from deep-sea organisms using alchemical free energy calculations and Archimedean displacement volumes.

[1] J. Roche et al, Proc. Natl. Acad. Sci. USA, 109, 6945-6950 (2012) [2] Y. Ma et al, Nature, 458, 182-185 (2009) [3] P. Loubeyre et al, Nature, 577, 631-645 (2020)