In the current study an innovative method of structural filtration of docked ligand poses is introduced and applied to improve the virtual screening results. The structural filter is defined by a protein-specific set of interactions that are a) structurally conserved in available structures of a particular protein with its bound ligands, and b) that can be viewed as playing the crucial role in protein-ligand binding. The concept was evaluated on a set of 10 diverse proteins, for which the corresponding structural filters were developed and applied to the results of virtual screening obtained with the Lead Finder software. The application of structural filtration resulted in a considerable improvement of the enrichment factor ranging from several folds to hundreds folds depending on the protein target. It appeared that the structural filtration had effectively repaired the deficiencies of the scoring functions that used to overestimate decoy binding, resulting into a considerably lower false positive rate. In addition, the structural filters were also effective in dealing with some deficiencies of the protein structure models that would lead to false negative predictions otherwise. The ability of structural filtration to recover relatively small but specifically bound molecules creates promises for the application of this technology in the fragment-based drug discovery.