C. Detering, C. Lemmen, M. Lilienthal, and M. Gastreich

We report on strengths and challenges of the Single Interaction Scan (SIS), a placement strategy that has recently been implemented into the well established ligand docking software FlexX. The method uses only a single interaction within the active site to accurately place the very first fragment of an incremental build-up process.

For cases in which few or no hydrogen bonds are formed between ligand and protein, the method has shown to provide a significant rise in accuracy compared to the existing algorithms implemented.

Typical application scenarios include hydrophobic pockets, lipophilic ligands, or bonding to metals, for example in cytochromes. For the latter, the coordination chemistry is fully taken into account on-the-fly. The SIS algorithm has been added to FlexX's two existing base placement strategies, including an extensive parameterization on validated, high quality datasets.