Free-energy calculations in the framework of classical molecular dynamics simulations are
nowadays used in a wide range of research areas including solvation thermodynamics …

▪ Abstract This article reviews the concepts and methods of transition path sampling. These
methods allow computational studies of rare events without requiring prior knowledge of …

Markov (state) models (MSMs) and related models of molecular kinetics have recently
received a surge of interest as they can systematically reconcile simulation data from either …

The recent availability of long equilibrium simulations of protein folding in atomistic detail for
more than 10 proteins allows us to identify the key interactions driving folding. We find that …

Characterizing the equilibrium ensemble of folding pathways, including their relative
probability, is one of the major challenges in protein folding theory today. Although this …

The “protein folding problem” consists of three closely related puzzles:(a) What is the folding
code?(b) What is the folding mechanism?(c) Can we predict the native structure of a protein …

Quantitatively accurate all-atom molecular dynamics (MD) simulations of protein folding
have long been considered a holy grail of computational biology. Due to the large system …

Despite the biological importance of protein–protein complexes, determining their structures
and association mechanisms remains an outstanding challenge. Here, we report the results …

The dissociation of a water molecule in liquid water is the fundamental event in acid-base
chemistry, determining the pH of water. Because of the short time scales and microscopic …

In this chapter we present the foundations and methodology of transition path sampling
comprehensively, including details important for its implementation. We first discuss the …