title: Enhancing Important Fluctuations: Rare Events and Metadynamics from a Conceptual Viewpoint.
abstract: Atomistic simulations play a central role in many fields of science. However, their usefulness is often limited by the fact that many systems are characterized by several metastable states separated by high barriers, leading to kinetic bottlenecks. Transitions between metastable states are thus rare events that occur on significantly longer timescales than one can simulate in practice. Numerous enhanced sampling methods have been introduced to alleviate this timescale problem, including methods based on identifying a few crucial order parameters or collective variables and enhancing the sampling of these variables. Metadynamics is one such method that has proven successful in a great variety of fields. Here we review the conceptual and theoretical foundations of metadynamics. As demonstrated, metadynamics is not just a practical tool but can also be considered an important development in the theory of statistical mechanics.
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zurich, c/o Università della Swizzera Italiana Campus, 6900 Lugano, Switzerland; email: parrinello@phys.chem.ethz.ch.|Facoltà di Informatica, Instituto di Scienze Computationali, Università della Svizzera Italiana, 6900 Lugano, Switzerland.
authors.forename: Omar
authors.initials: O
authors.lastname: Valsson
authors.affiliation: Department of Chemistry, Columbia University, New York, NY 10027.
authors.forename: Pratyush
authors.initials: P
authors.lastname: Tiwary
authors.affiliation: Department of Chemistry and Applied Biosciences, ETH Zurich, c/o Università della Swizzera Italiana Campus, 6900 Lugano, Switzerland; email: parrinello@phys.chem.ethz.ch.|Facoltà di Informatica, Instituto di Scienze Computationali, Università della Svizzera Italiana, 6900 Lugano, Switzerland.
authors.forename: Michele
authors.initials: M
authors.lastname: Parrinello
keywords: atomistic simulations; collective variables; enhanced sampling; free energy calculations; kinetic bottlenecks; kinetic rate calculations