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Abstract Satellite tobacco mosaic virus (STMV) is a model system for studying viral assembly and stability due to its architecture: a single-stranded RNA genome enclosed in an icosahedral capsid. Coupling a polarizable force-field to enhanced sampling, we explored at high-resolution the long-timescale structural dynamics of a complete ∼1M-atom STMV. RNA-free capsids exhibit remarkable stability at physiological salt concentrations, suggesting an evolutionary adaptation for capsid reuse during the viral life cycle. This observation challenges the notion that empty capsids are exclusively products of abortive assembly, positioning them instead as functional intermediates in viral reproduction. Additionally, RNA encapsidation creates electrostatic dependencies that magnesium ions mitigate, stabilizing both RNA and capsid through long-residence-time interactions with phosphate groups. Chloride ions further influence capsid permeability by modulating salt-bridge disruptions and interprotomeric interactions, with these effects being pH-dependent: enhanced at pH < 7, preserving nucleocapsid integrity, or weakened at pH = 7, facilitating disassembly and RNA release. 

Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid–base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids. The use of Parallel Java and OpenMM combines to offer shared memory, message passing, and graphics processing unit parallelization for high performance simulations. Overall, the FFX platform serves as a computational microscope to study systems ranging from organic crystals to solvated biomolecular systems. 

In the Big Data era, a change of paradigm in the use of molecular dynamics is required. Trajectories should be stored under FAIR (findable, accessible, interoperable and reusable) requirements to favor its reuse by the community under an open science paradigm.