Simulating biomolecules for physiological timescales

Advances in structural biology are providing many opportunities to simulate complex conformational motions in large-scale assemblies. While some models are limited by computational resources, all-atom and coarse-grained structure-based models have been particularly effective at elucidating mechanistic, energetic, and kinetic properties of collective rearrangements. Here, we highlight recent examples where structure-based models (e.g. "SMOG" models) have provided insights into long-timescale dynamics of large-scale processes. These models are sufficient to predict all structural characteristics of the energy landscape, where the use of explicit-solvent simulations has allowed for precise calibration of energetics and kinetics. Together, long-timescale simulations of complex assemblies, such as viral fusion proteins or the ribosome, are revealing how a balance of energetics and structural disorder drives biological and disease processes.