Current Virtual Screening methods (Docking, Pharmacophore, etc) can screen a large database of chemical compounds and rank them according to some computed score value. Usually one computationally screens a database containing millions of ligands against a given target, and selects a small fraction of the top scoring molecules, so they can be tested experimentally.
Sometimes such methods work, and some ligands bind stronger or weaker than predicted to the protein target. But it most cases, the functional consequence of ligand binding to the protein is not or can not currently be predicted; for instance, for a given ligand some rearrangement could happen in the other part of the protein, which would affect enormously to its biological function, while for some other ligand, the measure affinity could be of the same order of magnitude, but the functional consequences could be completely different.
So my questions here is; do you think in such scenario (ligand database virtual screening), and although affinity could be more or less estimated, can protein functionality (after ligand binding) predicted? And, which are the best tools/related-publications nowadays?