Milestoning is an approach for estimating the characteristic time scales of slow processes by combining data from many short simulations.

In the milestoning method, progress along a reaction coordinate is partitioned by creating a set of points, or hypersurfaces. Many short, independent trajectories are simulated, and the probability and mean first passage time for reaching an adjacent milestone are calculated to find the stationary flux across milestone boundaries. By considering all milestones along a reaction coordinate, the characteristic time scale for this transition can be obtained.

For the details of milestoning theory, see Faradjian and Elber, (2004) and West et al., (2007).

For examples of previously performed studies in which Milestoning was the primary method used, see the following example cases:

- Predicting Ligand Binding Kinetics Using a Markovian Milestoning with Voronoi Tessellations Multiscale Approach.
- Weighted ensemble milestoning (WEM): A combined approach for rare event simulations.
- Transient States and Barriers from Molecular Simulations and the Milestoning Theory: Kinetics in Ligand-Protein Recognition and Compound Design.
- ScMile: A Script to Investigate Kinetics with Short Time Molecular Dynamics Trajectories and the Milestoning Theory.
- Quantitative Ranking of Ligand Binding Kinetics with a Multiscale Milestoning Simulation Approach.
- SEEKR: Simulation Enabled Estimation of Kinetic Rates, A Computational Tool to Estimate Molecular Kinetics and Its Application to Trypsin-Benzamidine Binding.
- Multiscale Estimation of Binding Kinetics Using Brownian Dynamics, Molecular Dynamics and Milestoning.

Milestoning was also used in the following examples: