Where do we go from here? Current state of drug–target binding kinetics and a roadmap to their establishment in drug discovery campaigns

Because of the observation that kinetic rates can be better correlated with in vivo drug efficacy than simple affinities, significant efforts have been made to develop experimental and computational methods to predict drug-target residence times over the past few years. Here, we summarize the discussions and reflections from an international Centre Européen de Calcul Atomique et Moléculaire (CECAM) Workshop, which took place in March 2025, with participants from both academia and industry, including experimentalists as well as computational scientists, and was dedicated to computational methods for protein-ligand binding kinetics prediction. As currently standing challenges, we identify the need for standardized benchmark datasets, the need to move from simple to more complex and biomedically relevant targets and the question of how academia and industry can work together to move the field of drug-target binding kinetics forward. We also discuss what level of accuracy can be expected from computational methods and highlight that the field would benefit from blind challenges to enable a fair comparison of different computational methods to predict kinetic rates.