Use of metal coordination geometry to improve FlexX docking

COMP 327

Andreas Kämper, akaemper@mpi-inf.mpg.de, Susanne Pfeifer, and Thomas Lengauer, lengauer@mpi-inf.mpg.de. Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Stuhlsatzenhausweg 85, D-66123 Saarbrücken, Germany
Metalloproteins are valuable targets in structure-based drug design. A characteristic property of all metal ions is their coordination chemistry, i.e. the geometrical arrangements in which they bind to ligating atoms of proteins and small molecules. The current representation of metal ions in the docking program FlexX was replaced by a more accurate model by incorporating the correct coordination geometries for all biologically relevant metal ions. The implementation deals with all possible coordination geometries (ideal and distorted polyhedra), which are automatically generated from Protein Data Bank files. Here, also missing corners (which are occupied by ligand or water molecules) are taken into account. Interaction geometries are generated using a novel set of user-editable rules. Docking results on a large test set with the new metal ion description reveal a major improvement in the placement in most cases. Furthermore, docking is sped up significantly.