Pre-generated conformations

Three-dimensional alignment incorporates the problem of conformational flexibility. One possibility to address the problem is to pre-generate conformations (like in DISCO or Catalyst ), which makes the actual alignment less time-consuming, but the user has to ensure that all relevant conformations are included. On the other hand, there are in-process approaches that perform the pattern identification and conformational search simultaneously. 

DISCO, developed by Yvonne Martin s group at Abbott, and the HipHop [24] module of Catalyst, rely upon pre-calculated conformers. For DISCO these can be generated using a standard modeling package. The Catalyst suite includes a mod-... 

This effect is particularly well documented for y - and -amino acid residues [217, 218] which in several natural products (bleomycin A2 [219], calyculins [220]) have been shown to play a substantial role in the pre-organization of the whole molecule into its bioactive conformation. For example, changes in the substitution pattern of the y-amino acid linker in bleomycin A2 result in reduced DNA cleavage efficiency [219]. In the case of y-peptides, changing the relative configuration like or unlike of y " -amino acids has been used as a strategy to generate different local conformations (Fig. 2.34) suitable either for the construction of helices [201] or turns ]202-204]. 

In an alternative approach, MIP membranes can be obtained by generating molec-ularly imprinted sites in a non-specific matrix of a synthetic or natural polymer material during polymer solidification. The recognition cavities are formed by the fixation of a polymer conformation adopted upon interaction with the template molecule. Phase inversion methods have used either the evaporation of polymer solvent (dry phase separation) or the precipitation of the pre-synthesised polymer (wet phase inversion process). The major difficulties of this method lay both in the appropriate process conditions allowing the formation of porous materials and recognition sites and in the stability of these sites after template removal due to the lack of chemical cross-linking. 

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