An Integrated Markov State Model and Path Metadynamics Approach To Characterize Drug Binding Processes.

Unveiling the mechanistic features of drug-target binding is of central interest in biophysics and drug discovery. Herein, we address this challenge by combining two major computational approaches, namely, Molecular Dynamics (MD) simulations and Markov State Models (MSM), with a Path Collective Variables (PCVs) description coupled with metadynamics. We apply our methodology to reconstruct the binding process of the antagonist alprenolol to the β