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Beginning with the three-dimensional structure of the receptor, our docking algorithm identifies potential interaction partners inside the binding-site and represents them using appropriate interaction geometries (click here). By modeling chemical aspects of the docking problem directly, we avoid generating solutions which are meaningful only geometrically but not chemically. The flexibility of the ligand molecule is modeled by discrete sets of torsion angles for each rotatable bond and discrete sets of ring conformations for each ring system. Torsion angles are assigned using the MIMUMBA [KM94] data base. For the computation of ring system conformation, we use the programm SCA [HC88,HCC89]. To get a feeling for ligand flexibility, we have prepared pictures of 20 randomly generated conformations of a drug molecule.
In order to handle ligand flexibility, a small part of the ligand, called the base
fragment, is placed first. This process uses algorithms that are adapted from computer
vision [RWL96]. Subsequently, the ligand is re-constructed
incrementally inside the binding-site.
Efficient algorithms and data structures for three-dimensional range queries, for the
storage of partial placements, and for evaluating the energy function have been developed,
in order to reduce the time and space requirements [RWL95,RKL96].
Example
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