Validating the CHARMM36m protein force field with LJ-PME reveals altered hydrogen bonding dynamics under elevated pressures

The pressure-temperature phase diagram is important to our understanding of the physics of biomolecules. Compared to studies on temperature effects, studies of the pressure dependence of protein dynamic are rather limited. Molecular dynamics (MD) simulations with fine-tuned force fields (FFs) offer a powerful tool to explore the influence of thermodynamic conditions on proteins. Here we evaluate the transferability of the CHARMM36m (C36m) protein force field at varied pressures compared with NMR data using ubiquitin as a model protein. The pressure dependences of J couplings for hydrogen bonds and order parameters for internal motion are in good agreement with experiment. We demonstrate that the C36m FF combined with the Lennard-Jones particle-mesh Ewald (LJ-PME) method is suitable for simulations in a wide range of temperature and pressure. As the ubiquitin remains stable up to 2500 bar, we identify the mobility and stability of different hydrogen bonds in response to pressure. Based on those results, C36m is expected to be applied to more proteins in the future to further investigate protein dynamics under elevated pressures. Enzymes may behave differently at high pressures found in environments such as the ocean floor, but molecular dynamics force fields are not well characterized at high pressures. Here the CHARMM36m force field is validated against NMR data at variable pressures up to 2500 bar, using ubiquitin as a model protein.

Automated summary

The pressure-temperature phase diagram plays a crucial role in understanding the physics of biomolecules. The transferability of the CHARMM36m protein force field has been evaluated under different pressures, showing good agreement with experimental data and suitability for exploring protein dynamics. The study highlights the potential application of CHARMM36m in investigating protein behavior under elevated pressures.