Host-Guest Binding Free Energies à la Carte: An Automated OneOPES Protocol.

Estimating absolute binding free energies from molecular simulations is a key step in computer-aided drug design pipelines, but the agreement between computational results and experiments is still very inconsistent. Both the accuracy of the computational model and the quality of the statistical sampling contribute to this discrepancy, yet disentangling the two remains a challenge. In this study, we present an automated protocol based on OneOPES, an enhanced sampling method that exploits replica exchange and can accelerate several collective variables to address the sampling problem.