Retrovirology through the lens of the computational microscope.

The essential conundrum of modern biology, namely the question of how life emerges from myriad molecules whose behavior is governed by physical law alone, is embodied within a single cell—the quantum of life. The rise of scientific supercomputing has allowed for the study of the living cell in unparalleled detail, from the scale of the atom to a whole organism and at all levels in between. In particular, the past three decades have witnessed the evolution of molecular dynamics (MD) simulations as a “computational microscope”, which has provided a unique framework for the study of the phenomena of cell biology in atomic (or near-atomic) detail.  Our work synergistically combines single-molecule biophysics, structural biology and machine learning techniques to probe the molecular origin of biological phenomena. Here I present an overview of our synergistic efforts with experimentalists to determine the molecular details during the life-cycle of HIV-1. Our work reveals complex relationships between capsid permeability, mechano-elasticity and reverse-transcription, and deciphers the role of cellular host-factors during the life-cycle of the virus.