A recursive algorithm for efficient combinatorial library docking

MATTHIAS RAREY* and THOMAS LENGAUER

GMD - German National Research Center for Information Technology, Institute for Algorithms and Scientific Computing (SCAI), SchloƟ Birlinghoven, D-53754 Sankt Augustin, Germany

Summary. Due to the rapid development of combinatorial chemistry and high throughput screening, a new virtual screening scenario emerged. While previously the focus was on analyzing large collections of compounds available to the medicinal chemist, nowadays the search space is defined in the form of large, possibly virtual, combinatorial libraries. In this article we describe how the structure of combinatorial libraries can be exploited to speed up docking predictions. Based on our incremental construction method implemented in the docking software FLEXX we developed a recursive scheme to traverse the combinatorial library space efficiently. We applied our docking algorithm to three libraries with sizes from a few hundred up to 20 000 molecules. In all cases, we are able to show that similar results are achieved as in a sequential docking ofthe library molecules. The computing time, however, can be reduced by a factor of up to 30 resulting in an average time of about 5 s per library molecule.

Key words: combinatorial docking, combinatorial libraries, conformational analysis, drug design, molecular docking, receptor ligand interaction

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