Efficient conformational sampling and weak scoring in docking programs? Strategy of the wisdom of crowds.

We conclude that the scoring functions should be improved to detect the correct poses, but sometimes their failure may be due to other varied considerations. To increase the chances of success, we recommend to use several programs and combine their results. Graphical abstract Summary of the results obtained by semi-rigid docking of crystallographic ligands. The docking was done on 100 protein-ligand X-ray structures, taken from the DUD-E database, and using four programs, Glide, Gold, Surflex and FlexX. Based on the docking results, we applied our United Subset Consensus method (USC), for which only the top4-rank poses are relevant. The number of complexes for which the best pose is correct, is represented by the gray boxes, the blue and red boxes correspond to the number of complexes with a correct pose ranked as the top 1 or within the top 4. A pose is considered correct when its root-mean-square deviation from the crystal structure is less than 2 Å.