Packaging of nucleic acids is essential for all life, occurring across diverse scales and complexities. Virus particles, with their dense packaging, allow us to study fundamental packaging principles. I will begin by introducing a multi-resolution (MR) approach to determine the complete structure of bacteriophage HK97, including its 39,732 base pair genome [1]. Mimicking the action of a packaging motor, we simulated genome loading and refined the packaged capsid structure at increasing resolutions, generating a 26 million atom model of the entire virion, including internal water and ions. Surprisingly, our simulations reveal a loop extrusion mechanism for DNA packaging, resulting in diverse genome configurations and unique viral particle attributes. Microsecond-long all-atom simulations explored the packaged genome’s impact on capsid structure, internal pressure, electrostatics, and the diffusion of water, ions, and DNA. This adaptable methodology can be applied to other dsDNA viruses, like herpes. I will then broaden the scope to discuss my ongoing work on fundamental molecular dynamics methodology. The integration time step remains a primary bottleneck for achieving sufficient sampling; however, increasing it introduces numerical biases, meaning we no longer sample the intended potential energy surface. I will present my recently submitted work [2] demonstrating that this sampled "shadow Hamiltonian" acts as an effective linear perturbation, and that using a simple thermodynamic model, we can extrapolate observables to the zero-time-step limit and Boltzmann “correct” the inaccurately sampled distributions. Importantly, these corrections are critical for ensuring the reliability of enhanced sampling methods that rely on accurate energies and temperatures for statistical reweighting.