Abstract
Equilibrium sampling of biomolecules remains an unmet challenge after more than 30 years of atomistic simulation. Efforts to enhance sampling capability, which are reviewed here, range from the development of new algorithms to parallelization to novel uses of hardware. Special focus is placed on classifying algorithms--most of which are underpinned by a few key ideas--in order to understand their fundamental strengths and limitations. Although algorithms have proliferated, progress resulting from novel hardware use appears to be more clear-cut than from algorithms alone, due partly to the lack of widely used sampling measures.