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

You Xu,Jing Huang

doi:10.1038/s42004-021-00537-8

Abstract

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.

Highlights

The pressure-temperature phase diagram is important to our understanding of the physics of biomolecules
As all ubiquitin simulations presented in this study were carried out using the Lennard-Jones particle-mesh Ewald (LJ-particle-mesh Ewald (PME)) method with OpenMM, we first performed some validation studies
The major purpose of this study is to evaluate the capability of CHARMM36m additive force field combined with the LJ-PME nonbonded method in a wide range of temperature and pressure

Summary

Introduction

The pressure-temperature phase diagram is important to our understanding of the physics of biomolecules. While the temperature influence on protein conformational dynamics has been extensively investigated, studies on the protein structure and function at high pressures are relatively rare. Simulations have been applied to folded proteins and intrinsically disordered proteins, as well as proteins under complicated but functionally important environments such as multicomponent membranes[6,7], phase separated states[8,9], and crowded environment in cells[10,11]. The quality of these simulations depends critically on their underlying models, typically the empirical force fields. Through-space scalar coupling h3JNC’ detects the strength of protein backbone hydrogen bond (H-bond) N–H···O=C between two residues[22,23] and provides information for both the local H-

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