Using Ligand‐Mapping Simulations to Design a Ligand Selectively Targeting a Cryptic Surface Pocket of Polo‐Like Kinase 1

Abstract

An explicit solvent ligand-mapping approach was used to reveal an otherwise hidden hydrophobic pocket in polo-like kinase 1 (Plk1). It predicted a novel ligand binding mode that was used for the design of a new ligand with high affinity for Plk1. X-ray crystallography confirmed that the binding was specific to the intended pocket.