Preparation of target CETP in docking-based virtual screening

When conducting docking-based virtual screening, we should carefully prepare the target protein. Generally, the ligands coupled with the receptor-ligand complex are often deleted from the crystal structure, but it is unknown that in which situation the ligands should be deleted. Taking CETP for example, this study conducted virtual screening against CETP through 2 different styles. In style 1, the cholesteryl ester near the active site was deleted. In style 2, the cholesteryl ester was kept to conduct the virtual screening. We found that the results were very different from each other and style 2 was the preferable choice in this situation. The reason why like this is that there is strong repulsion between drug molecule and the cholesteryl ester.