Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein–Ligand Binding

We present a reliable and accurate solution to the induced fit docking problem for protein–ligand binding by combining ligand-based pharmacophore docking, rigid receptor protein structure prediction with explicit solvent molecular dynamics simulations. This novel methodology in detailed retrospective prospective testing succeeded determine modes root-mean-square deviation within 2.5 Å over 90% of cross-docking cases. further demonstrate these predicted ligand–receptor structures were sufficiently prospectively enable predictive structure-based drug discovery challenging targets, substantially expanding domain applicability such methods.