S. Hindle, C. Detering, M. Gastreich, and H. Claußen

Despite the good quality in uploaded protein structures, there are still uncertainties when it comes to defining an active site. The correct physico-chemical surrounding of a ligand can be crucial though in molecular docking and screening. E.g. defining metal atoms as pharmacophores, assigning an alternative amino acid and protonation state and the correct insertion and orientation of (displaceable) water molecules all play a vital role in the preparation of an active site for docking. Also, it might be necessary to scale the contribution of certain interactions to the overall score.
We show recent advances to prepare an active site for docking and screening and show a few proof-of-concepts.