Docking of combinatorial libraries

FlexX An extension of the FlexX docking program which increases the efficiency of the docking of combinatorial libraries Tripos, Inc. http //www.tripos.com [32]... 

Owing to the much longer per-molecule computing time, exploiting the structure of combinatorial libraries becomes much more important for molecular docking algorithms. 

In the context of combinatorial libraries, we distinguish between three kinds of docking problems ... 

An alternative to sequential docking can be followed if combinatorial libraries are evaluated. Quite a few programs have been specifically designed for speed-up by so-called combinatorial docking. They profit from the structured, incremental nature of combinatorial libraries and the fact that molecules of a combinatorial library consist of a common core. This core is assumed to form common specific interactions with the receptor (possibly supported by experimental evidence) and can thus be prepositioned in the binding pocket in one or a few similar orientations. It then serves as skeleton for the addition of substituents. Obviously, this step is ideally suited for incremental construction algorithms (361)... 

This paper is divided into three parts. First, the different steps in the molecular docking process are described. Second, we discuss ligand databases. Finally, we close with a few success stories of the structure-based methodology. We also describe the way structure-based design has been an aid in the construction of combinatorial libraries. 

Leach, A.R., and Taylor, R. Further development of a genetic algorithm for ligand docking and its application to screening combinatorial libraries. ACS Symp. Ser. Am. Chem. Soc. 1999, 719, 271-291. 

Fragment-based design, where the constituents of the compounds (scaffolds and functional groups/substituents) are docked in the binding site and then linked together to build combinatorial libraries. 

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