Buckets Instead of Umbrellas for Enhanced Sampling and Free Energy Calculations.

Umbrella sampling has been a workhorse for free energy calculations in molecular simulations for several decades. In conventional umbrella sampling, restraining bias potentials are strategically applied along one or several collective variables. Major drawbacks associated with this method are the requirement of a large number of bias windows and the poor sampling of the transverse coordinates.

Exploration of high dimensional free energy landscapes by a combination of temperature-accelerated sliced sampling and parallel biasing.

Temperature-accelerated sliced sampling (TASS) is an enhanced sampling method for achieving accelerated and controlled exploration of high-dimensional free energy landscapes in molecular dynamics simulations. With the aid of umbrella bias potentials, the TASS method realizes a controlled exploration and divide-and-conquer strategy for computing high-dimensional free energy surfaces. In TASS, diffusion of the system in the collective variable (CV) space is enhanced with the help of metadynamics bias and elevated-temperature of the auxiliary degrees of freedom (DOF) that are coupled to the CVs.