Heat-induced transitions of an empty minute virus of mice capsid in explicit water: all-atom MD simulation

Abstract

The capsid-like structure of the virus-based protein nanoparticles (NPs) can serve as bionanomaterials, with applications in biomedicines and nanotechnology. Release of packaged material from these nanocontainers is associated with subtle conformational changes of the NP structure, which in vitro, is readily accomplished by heating. Characterizing the structural changes as a function of temperature may provide fresh insights into nanomaterial/antiviral strategies. Here, we have calculated heat induced changes in the properties of an empty minute virus of mice particle using large-scale ≈ 3.0 × 10⁶ all-atom molecular dynamics simulations. We focus on two heat induced structural changes of the NP, namely, dynamical transition (DT) and breathing transition (BT), both characterized by sudden and sharp change of measured parameters at temperatures, T_DT and T_BT, respectively. While DT is assessed by mean-square fluctuation of hydrogen atoms of the NP, BT is monitored through internal volume and permeation rate of water molecules through the NP. Both the transitions, resulting primarily from collective atomistic motion, are found to occur at temperatures widely separated from one another (T_BT>T_DT). The breathing motions, responsible for the translocation events of the packaged materials through the NP to kick off, are further probed by computing atomic resolution stresses from NVE simulations. Distribution of equilibrium atomistic stresses on the NP reveals a largely asymmetric nature and suggests structural breathing may actually represent large dynamic changes in the hotspot regions, far from the NP pores, which is in remarkable resemblance with recently conducted hydrogen-deuterium exchange coupled to mass spectrometry experiment.

Communicated by Ramaswamy H. Sarma

Keywords:

• Viral capsid
• MD simulations
• heat-induced transitions
• breathing motion
• atomistic stress

Acknowledgments

The authors thank computer center, BARC for providing the ANUPAM parallel computational facility. The work was supported by DAE under project XII-N-R&D-02.04/Theoretical & Computational Chemistry of Complex Systems.

Author’s contribution

Arup Kumar Pathak: methodology, experiment. Tusar Bandyopadhyay: conceptualization, methodology, supervision, writing – review & editing.

Disclosure statement

There are no conflicts to declare.

Data availability statement

The pdb files of the final conformations of the three systems, i.e. isolated protein, capsomer, and the full capsid, in total with counterions and solvation box can be obtained from authors on request.