Protein structures in virtual screening: A case study with CDK2

The influence of protein structure on the successful reproduction of known ligand poses by high-throughput docking programs is rarely discussed. Two commonly used programs, Glide and GOLD, were used to dock a set of CDK2 inhibitors of known bound pose into 20 different CDK2 structures. The numbers of docked poses that reproduced the known pose are reported. Depending on the program and protein structure, 0.3%-96.2% of the ligands docked with the correct pose. Although it is not possible to say that any one structure is "the best" for virtual screening, there are some structures that are clearly better than others. The main determinants of this are the volume of the binding site into which the ligands are docked and the exact orientation of the residues forming, the binding site.