The dynamics of large biomolecular assemblies

With recent advances in cryo-electron microscopy/cryo-electron tomography (cryoEM/cryoET), computational capabilities and machine learning, there has been an incredible increase in the speed of structure determination for large biomolecular assemblies. In order to connect these static descriptions with biological function, one needs reliable and accurate approaches to quantify the factors that regulate dynamics. For this, models that employ simplified energetics and/or coarse-grained representations have become indispensable tools for integrating structural insights, biochemical analyses and physical principles. Here we discuss examples where molecular simulations have provided a framework for understanding dynamics in assemblies of increasing size and complexity. We focus on three classes for which there have been notable advances in recent years: ribosomes, viral capsids and nuclear pore complexes. Each possesses unique physical attributes that have required distinct theoretical and computational strategies. Together, these studies provide a rich conceptual and technical foundation that can help shape our perspective on the machinery of the cell.