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c36m.ljpme.ubiquitin.pdf (8.93 MB)

Validating the CHARMM36m Protein Force Field with LJ-PME Reveals Altered Hydrogen Bonding Dynamics under Elevated Pressures

preprint
revised on 30.05.2021, 12:02 and posted on 01.06.2021, 06:37 by You Xu, Jing Huang

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 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

LR19B030001 | Zhejiang Provincial Natural Science Foundation of China

LQ20C05001 | Zhejiang Provincial Natural Science Foundation of China

Study on the conformational ensemble and self-assembly of natural disordered proteins using polarizable molecular force fields

National Natural Science Foundation of China

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History

Email Address of Submitting Author

huangjing@westlake.edu.cn

Institution

Westlake University

Country

China

ORCID For Submitting Author

0000-0001-9639-2907

Declaration of Conflict of Interest

no conflict of interest

Version Notes

Version to be published in Communications Chemistry.