The ultimate goal for running large, parallelized MD simulation dataset is to generate a well-sampled ensemble picture of a biomolecular construct of interest. A well-sampled ensemble picture requires both a breadth of states to be discovered, as well as sufficient depth of sampling that multiple transitions are observed. Ideally, these transitions would be observed in both directions which would enable one to as-Chapter sess the statistical rarity of these conformational sampling events. However, many biologically relevant motions occur on much longer timescales in the hundreds of microseconds, milliseconds, and beyond . As such, even with equilibrium simulations, it can be challenging to observe biochemically relevant events that would be probed experimentally. Indeed, multiple studies have shown that standard equilibrium simulations are insufficient to sample the relevant landscape of structural states to generate useful hypotheses . To generate useful sampling of states in an accessible period of wall time, decades of effort have gone into developing enhanced sampling approaches that increase simulation sampling. These methods use physics-inspired and statistical approaches to discover new states, increase number of transitions observed, or cross slow-timescale kinetic barriers. Such approaches can span ranking promising states as starting configurations for future simulations, or altering the Hamiltonian of the system to increase state transition probabilities.