Exploiting Free‐Energy Minima to Design Novel EphA2 Protein–Protein Antagonists: From Simulation to Experiment and Return

Abstract

The free-energy surface (FES) of protein-ligand binding contains information useful for drug design. Here we show how to exploit a free-energy minimum of a protein-ligand complex identified by metadynamics simulations to design a new EphA2 antagonist with improved inhibitory potency.