Metadynamics as a Tool for Exploring Free Energy Landscapes of Chemical Reactions

Abstract

The metadynamics or hills method is a relatively new molecular dynamics technique aimed to enhance the sampling of separated regions in phase space and map out the underlying free energy landscape as a function of a small number of order parameters or collective variables. The high efficiency allows for the application of metadynamics in combination with first principles dynamics methods, in particular with Car-Parrinello molecular dynamics, to study processes in which changes in the electronic structure play a dominant role, such as chemical reactions. The option to choose several independent collective variables is important to tackle complex and concerted transformations that lack an obvious a priori choice for a single reaction coordinate. In this Account, we discuss the role of metadynamics in the search of transition states, local minima, reaction paths, free energy profiles, and reaction coordinates among a growing list of alternative methods.

Mapping the conformational free energy of aspartic acid in the gas phase and in aqueous solution

“…[26][27][28] Metadynamics has been successfully used to study a wide range of problems in the physical, chemical, biological, and material sciences. 26,[29][30][31][32][33][34] As metadynamics efficiency decreases with the number of biased CVs, the minimal CV set providing meaningful results should be chosen. To map the conformers of Asp, the three backbone torsional angles α, β, and γ are an obvious, but not adequate choice, as we observed with preliminary calculations.…”

The mechanism of formate oxidation by metal-dependent formate dehydrogenases

“…Several methods are available to study chemical reactions, including static quantum approaches or even advanced sampling techniques, e.g., umbrella sampling [21], metadynamics [22][23][24], and parallel tempering [25]. In this work, the reaction mechanism was explored using the static quantum approach [26].…”

Towards a Rational Design of Ruthenium CO2 Hydrogenation Catalysts by Ab Initio Metadynamics

“…It locally modifies the energy profile of those regions in the configurational space that have already been visited and thereby prevents the trajectory from hanging about in the same basin of attraction for very long time. [36] This approach enforces the exploration of the free energy surface and is able to disclose the most probable pathways of a reaction, even if no prior knowledge of the transition and of the products is available. The scope of the applications was significantly broadened by its implementation together with ab initio methods [24] , such as DFT-based Car-Parrinello MD [37] .…”