The exchange between metastable configurations of proteins and nucleic acids is essential to their biological function . Molecular dynamics (MD) simulations are widely adopted for simulating the transitions between metastable states because they offer full spatial and temporal resolution of molecular systems. These transitions can range from simple localized changes, such as aromatic ring-flips , to complex global structural rearrangements, including protein folding ; ; and protein-ligand binding ; ; ; . Experimental techniques that enable the measurement of signals sensitive to the exchange between these states ; ; ; have greatly advanced the study of these metastable states. However, low spatial resolution and ensemble averaging are still challenges that complicate data analyses .