Molecular dynamics methods which aim to simulate the spontaneous process of proteinligand binding have been in development for the last decade. Over this period, significant advancements have been made due to increased access to high-performance computing resources (in particular GPU accelerated hardware), improvements in computational hardware, and developments in MD algorithms. Thus far, work in the field has predominantly focused on determining the mechanism of ligand binding to crystallographically determined sites. The idea behind these efforts is that by observing the spontaneous process of binding to these sites, key metastable states and associated protein ligand contacts can be identified. It is hoped that these interactions can then be modulated to optimise the kinetic and thermodynamic properties of drug binding. Some of these studies have also led to the elucidation of non-experimentally determined sites, which may act as allosteric sites for the modulation of protein activity.