We also found that the matched receptor and guidance generally outperformed the consensus density guidance for the screening application (See Tables ). This is in contrast to the greater improvement seen in cross-docking pose prediction from the consensus density guidance. We hypothesize this is due to the differences in the tasks of pose prediction and active/inactive discrimination in multiple receptor structures. For cross-dockings, we likely need a somewhat less specific guidance force to accommodate the slight differences between the native and cross-docked holo receptors for the ligand being tested. This would also explain the improvement seen with the degraded density guidance. However, discrimination between actives and inactives within a receptor ensemble is distinct from these cross-docking tasks in that each ligand is only scored for the best matched receptor state and density, rather than needing a single structure capable of accommodating all ligands. As a result, an exact pairing of a receptor state to its density its preferable to integrating all density into a single state. The same concept holds true for re-docking as well, where success rate is the same between the matched and consensus density guidance for ALK (Fig. ), and the matched guidance is better for re-docking for µOR and HIV-1 intasome (Fig. and Fig. ).