On the convergence improvement in the metadynamics simulations: A Wang-Landau recursion approach

Abstract

As a popular tool in exploring free energy landscapes, the metadynamics method has been widely applied to elucidate various chemical or biochemical processes. As deeply discussed by Laio et al. [J. Phys. Chem. B 109, 6714 (2005)], the size of the updating Gaussian function is pivotal to the free energy convergence toward the target free energy surface. For instance, a greater Gaussian height can facilitate the quick visit of a conformation region of interest; however, it may lead to a larger error of the calculated free energy surface. In contrast, a lower Gaussian height can guarantee a better resolution of the calculated free energy surface; however, it will take longer time for such a simulation to navigate through the defined conformational region. In order to reconcile such confliction, the authors present a method by implementing the Wang-Landau recursion scheme in the metadynamics simulations to adaptively update the height of the unit Gaussian function. As demonstrated in their model studies on both a toy system, and a realistic molecular system treated with the hybrid quantum mechanical and molecular mechanical (QMMM) potential, the present approach can quickly result in more decently converged free energy surfaces, compared with the classical metadynamics simulations employing the fixed Gaussian heights.