Abstract: The essential conundrum of modern biology, namely the question of how life emerges from myriad molecules whose behavior is governed by physical laws alone, is embodied within a single cell—the quantum of life. The rise of scientific supercomputing has enabled the study of the living cell in unparalleled detail, spanning from the scale of the atom to a whole organism and at all levels in between. As a result, the past three decades have witnessed the evolution of molecular dynamics (MD) simulations as a "computational microscope," providing a unique framework for the study of the phenomena of cell biology in atomic (or near-atomic) detail. The work in my group synergistically combines single-molecule biophysics, structural biology, and computational biology techniques to probe the molecular origin of biological phenomena. Here, I present an overview of our recent efforts to determine the molecular details during the life cycle of a human pathogen: HIV-1. Our research uncovers intricate connections among the physical properties of the virus during two key infection events, namely cytoplasmic trafficking and nuclear entry. We validate our discoveries through in vivo infectivity assays on multiple cell lines to confirm their biological relevance. Altogether, the results from our work unveil the roles of essential cellular machinery in the virus life cycle, paving the way for the design of novel therapeutics. Lastly, I discuss the adaptability of our integrative computational-experimental methods to decode the molecular mechanisms of tumor viruses.