Three-dimensional structure searching conformational flexibility

Experience has shown that retrieval based on 3D geometric cues often returns structures in very different chemical classes as compared with the compound from which the query originated. For additional information see also Conformational Flexibility in 3D Structure Searching and Three-dimensional Structure Searching. 

The size of a conformational search space defined by spatial relations among nitrogen bases is smaller than a conformational search space defined by backbone torsion angles. Mainly because of the theoretical flexibility of the backbone, a conformational search space defined by backbone torsion angles produces a very large number of three-dimensional structures of high uncertainty in the position and orientation of the nitrogen bases. 

ChemCore module to three-dimensionalize 2D structures, interfaces to reformat MACCS, SMILES, or DARC-2D databases, ChemDBS-1 module to build 3D databases, and ChemDBS-3D module to search 3D databases. Database searching accounts for conformational flexibility while storing only one conformation. Chapman 8c Hall s 3D Dictionary of Drugs (12,000 medicinally interesting compounds), 3D Dictionary of Natural Products (50,000 antibiotics, alkaloids, and terpenoids), and 3D Dictionary of Fine Chemicals (105,000 organics). 

Clark, D.E., Willett, P. and Kenny, P. (1992). Pharmacophoric Pattern Matching in Files of Three-Dimensional Chemical Structures Use of Smoothed-Bounded Distance Matrices for the Representation and Searching of Conformationally-Flexible Molecules. J.MoLGraphics, 10,194-204. 

Clark DE, Willett P, Kenny PW. Pharmacophoric pattern matching in files of three-dimensional chemical structures use of bounded distance matrices for the representation and searching of conformationally flexible molecules. J Mol Graph 1992 10 194-204. 

Pharmacaphoric Pattern Matching in Files of Three-Dimensional Chemical Structures Comparison of Conformational-Searching Algorithms for Flexible Molecules. 

Second, the work to date has taken only limited account of conformational flexibility. Although this can be overcome, to some extent, by calculating and storing all of the low-energy conformations in the search file, this is feasible only when there are few such conformations. We believe it likely that a precise definition of conformational flexibility will require forms of structural representation that go far beyond the current types of three-dimensional connection table, e.g., the use of approaches derived from distance geometry. ... 

D. E. Clark, G. Jones, and P. Vi illett, /. Chem. Inf. Comput. Set., 34, 197 (1994). Pha macophoric Panern Matching in Files of Three-Dimensional Chemical Structures Comparison of Conformational Searching Algorithms (or Flexible Searching. 

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