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All too frequently it occurs in drug design that no structural information on the receptor is available. Often, only a set of ligands with their binding affinity to a common receptor and the amino-acid sequence of the receptor protein is given and the question is: What are the important functional groups interacting with the receptor and what are their relative positions in the complex ? Such an arrangement of interacting groups is called a pharmacophore. There are several approaches known for solving this problem. One class of approaches is called QSAR (quantitative structure activity relationships [K93]). A central point within this context is the relative orientation of the ligands in the complex. Thus we are faced with the problem of aligning small molecules structurally without knowing the intermolecular relationships of the chemically relevant groups of each ligand. Superposition methods that map and compare shape and field properties of the molecules appear to be suited for revealing relevant structural alignments. Most of the techniques that superimpose molecules by exploiting their field properties are reported to be computationally intensive and rather slow. That is why efficient algorithms are strongly needed in this field. As in the docking problem, the explicit consideration of conformational flexibility is an additional task with a combinatorial character.
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