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.

Funding source: Zhejiang Provincial Natural Science Foundation of China (Grant No. LR19B030001 and LQ20C050001), National Natural Science Foundation of China (Grant No. 21803057), Westlake Education Foundation and Tencent Foundation.

Article metrics loading...



Supplemental Material

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error