Using metadynamics to explore complex free-energy landscapes

Metadynamics is an atomistic simulation technique that allows, within the same framework, acceleration of rare events and estimation of the free energy of complex molecular systems. It is based on iteratively \u2018filling\u2019 the potential energy of the system by a sum of Gaussians centred along the trajectory followed by a suitably chosen set of collective variables (CVs), thereby forcing the system to migrate from one minimum to the next. The power of metadynamics is demonstrated by the large number of extensions and variants that have been developed. The first scope of this Technical Review is to present a critical comparison of these variants, discussing their advantages and disadvantages. The effectiveness of metadynamics, and that of the numerous alternative methods, is strongly influenced by the choice of the CVs. If an important variable is neglected, the resulting estimate of the free energy is unreliable, and predicted transition mechanisms may be qualitatively wrong. The second scope of this Technical Review is to discuss how the CVs should be selected, how to verify whether the chosen CVs are sufficient or redundant, and how to iteratively improve the CVs using machine learning approaches

Time-dependent density functional theory calculations of near-edge X-ray absorption fine structure with short-range corrected functionals

We report calculations of core excitation energies and near-edge X-ray absorption fine structure (NEXAFS) spectra computed with time-dependent density functional theory (TDDFT). TDDFT with generalized gradient approximation and standard hybrid exchange-correlation functionals is known to underestimate core excitation energies. This failure is shown to be associated with the self-interaction error at short interelectronic distances. Short-range corrected hybrid functionals are shown to reduce the error in the computed core excitation energies for first and second row nuclei in a range of molecules to a level approaching that observed in more traditional excited states calculations in the ultraviolet region. NEXAFS spectra computed with the new functionals agree well with experiment and the pre-edge features in the NEXAFS spectra of plastocyanin are correctly predicted