Simulating large-scale dynamics in biomolecular assemblies

Biological function is frequently enabled large-scale molecular rearrangements. To establish a precise physical-chemical understanding of factors that control these processes, we develop and apply theoretical models that allow for the simulation of large-scale (10-300Å) rearrangements. To this end, all-atom structure-based “SMOG” models have been particularly effective at quantifying the energetics of collective rearrangements. Depending on the molecular system, we customize these models in order to determine what types of molecular interactions are most significant. Here, we describe recent advances to understand the roles of ions in large-scale assemblies, such as the ribosome, as well as efforts to study the conformational motions that enable host-virus membrane fusion.