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SIRAH_Packmol_draft_v12.pdf (2.09 MB)
Wrapping up Viruses at Multiscale Resolution: Optimizing PACKMOL and SIRAH Execution for Simulating the Zika Virus.
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
submitted on 14.10.2020 and posted on 15.10.2020by Martín Soñora, Leandro Martinez, Sergio Pantano, Matías R. Machado
Simulating huge biomolecular complexes of million atoms at relevant biological timescales is becoming
accessible to the broad scientific community. That proves to be crucial for urgent responses against
emergent diseases in real time. Yet, there are still some issues to be overcome regarding the system
setup so that Molecular Dynamics (MD) simulations can be run in a simple and standard way. Here, we
introduce an optimized pipeline for building and simulating enveloped virus-like particles (VLP). First,
the membrane packing problem is tackled with new features and optimized options in PACKMOL. This
allows to prepare accurate membrane models of thousands of lipids in the context of a VLP within a
few hours using a single CPU. Then the assembly of the VLP system is done within the multiscale
framework of the coarse-grained SIRAH force field. Finally, the equilibration protocol provides a
system ready for production MD simulations within a few days on broadly accessible GPU resources.
The pipeline is applied to study the Zika Virus as a test case for large biomolecular systems. The
multiscale scheme is well preserved along the simulation as evidenced from the radial distribution
function of each constituent. The VLP stabilizes at approximately 0.5 ms of MD simulation,
reproducing correlations greater than 0.90 against experimental density maps from cryo-electron
microscopy. Detailed structural analysis of the protein envelope also shows very good agreement in root
mean square deviations and B-factors with the experimental data. A rationale for a possible role of
anionic phospholipids in stabilizing the envelope is introduced. The presented pipeline can be
extrapolated to study other viral systems as well as intracellular compartments, paving the way to whole