Three-dimensional database searching

000 compounds, of which perhaps one-third are of potential pharmaceutical relevance. The other databases have 3D struaures generated by rule-based and other computational techniques. In-house databases are usually in the form of connection tables, that is, two-dimensional structural information recording which atoms are connected by bonds. 

Two factors contribute to the difficulty of searching 3D databases. First is the difficulty in specifying the search parameters. How are similar shapes defined Second, although the conformation stored in the database may be the most probable conformation (either the crystal structure or an energy minimum), in some cases a higher energy conformation is the biologically active one. Therefore, conformational flexibility should be included in the search process.Different methods have been developed to carry out searches in three dimensions. Detailed introductions to the problems and methods of 3D 

Three-dimensional database searching algorithms are available as add-on modules for some popular molecular modeling packages. An add-on module 

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DP Mamott, IG Dougall, P Meghani, Y-J Liu, DR Flower. Lead generation using pharmacophore mapping and three-dimensional database searching Application to muscarinic M3 receptor antagonists. J Med Chem 42 3210-3216, 1999. 

Kurogi Y, Miyata K, Okamura T, Hashimoto K, Tsutsumi K, Nasu M, Moriyasu M. Discovery of novel mesangial cell proliferation inhibitors using a three-dimensional database searching method. J Med Chem 2001 44 2304-7. 

SPLICE - a program to assemble partial query solutions from three-dimensional database searches into novel ligands. 

Kurogi, Y. and Guner, O.F. Pharmacophore modeling and three-dimensional database searching for dmg design using catalyst. Curr. 

Kaminski, J.J., Rane, D.F., Snow, M.E., Weber, L, and Rothofsky, M.L Identification of novel farnesyl protein transferase inhibitors using three-dimensional database searching methods./. Med. Chem. 1997, 40, 4103-4112. 

Greenidge, P.A., Carlsson, B., Biadh, L.G., and Gillner, M. Pharmacophores incorporating numerous excluded volumes defined by x-ray crystallographic structure in three-dimensional database searching application to the thyroid hormone receptor./. Med. Chem. 1998, 41, 2503-2512. 

Warr W. A., Willett P. The Principles and Practice of Three-Dimensional Database searching, in Design of Bioactive Molecules, American Chemical Society, Washington D.C., 1998,... 

Nicklaus, M.C., Neamati, N., Hong, H., Mazumder, A., Sunder, S., Chen, J. et al. (1997) HlV-1 integrase pharmacophore discovery of inhibitors through three-dimensional database searching. 

Kaminski JJ, Rane DF, Snow ME, Weber L, Rothofsky ML, Anderson SD, Lin SL. Identification of novel famesyl protein transferase inhibitors using three-dimensional database searching methods. J Med Chem 1997 40 4103 4112. 

Three-dimensional database searching of bioactive compounds and their application 00YGK676. 

Finn PW, Snarey M. Flexible three-dimensional database searching for the identification of novel lead compounds. In Bioactive Compound Design. Ford. Martyn G. (ed). Oxford. UK Bios Scientific Publishers. 1996 pp. 67-76. 

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