How can receptor flexibility invalidate a docking conclusion?

Why

A ligand might fit a crystal structure with an open active-site loop but clash in the solution ensemble, while another binds only after induced fit. Local loops, side chains and domain motions can all create meaningful conformational heterogeneity. Compare experimentally supported receptor states, run restrained ensemble docking when appropriate and consider molecular dynamics or induced-fit methods as hypothesis tools.

Check whether pocket opening occurs in biological conditions and whether scoring results are stable to receptor choice. For example, a narrow tunnel that appears blocked in an apo prediction may open when the substrate binds, yielding false negatives in rigid docking. Additional conformers add opportunities for false positives, so benchmark performance and confirm predictions experimentally.