Studying rare events using forward-flux sampling: Recent breakthroughs and future outlook

Rare events are processes that occur upon the emergence of unlikely fluctuations. Unlike what their name suggests, rare events are fairly ubiquitous in nature, as the occurrence of many structural transformations in biology and material sciences is predicated upon crossing large free energy barriers. Probing the kinetics and uncovering the molecular mechanisms of possible barrier crossings in a system is critical to predicting and controlling its structural and functional properties. Due to their activated nature, however, rare events are exceptionally difficult to study using conventional experimental and computational techniques. In recent decades, a wide variety of specialized computational techniques-known as advanced sampling techniques-have been developed to systematically capture improbable fluctuations relevant to rare events. In this perspective, we focus on a technique called forward flux sampling [Allen et al., J. Chem. Phys. 124, 024102 (2006)] and overview its recent methodological variants and extensions. We also provide a detailed overview of its application to study a wide variety of rare events and map out potential avenues for further explorations. Published under license by AIP Publishing.