Searching Databases of Three-Dimensional Structures

Yvonne C. Martin/ Mark G. Bures, and Peter Willett+ 

The emerging techniques for computer recognition of the similarity of three-dimensional properties of molecules will be discussed in this review. In particular, we will concentrate on methods or computer programs that examine a database of three-dimensional structures. However, to place such programs in context we will introduce the concepts of chemical information and the terminology, usually derived from molecular graphics, of three-dimensional similarity. Since much of the impetus for this research has been from research on computer-assisted design of bioactive molecules, this field will be introduced also. 

Three-dimensional structures of small molecules and macromolecules are being generated in record numbers. A database of the X-ray crystal structures of 70,000 small organocarbon compounds and another of several hundred protein and DNA struaures are available to scientists. Furthermore, it is often routine to experimentally determine the three-dimensional structure of a small molecule by single-crystal X-ray diffraction, and it is very easy to build on the computer a three-dimensional structure of a small molecule and to discover most if not all of its low-energy conformations. Finally, there is a 

Somewhat later, Marshall and co-workers showed that the bioactive conformation need not be the global minimum energy structure. Furthermore, they emphasized that in the small molecule-macromolecule complex, the macromolecule occupies certain regions in space near the small molecule (otherwise there would be no complex formed), and that thus one would expect to find certain molecules to be inactive because when juxtaposed they collide with the macromolecule. Most modeling studies of the bioaaivity of small molecules 

In summary, there exist large databases containing detailed structural information, and one can rapidly generate new databases of three-dimensional structures of small molecules using computational methods described in this book. Versatile programs for searching the three-dimensional data will allow chemists and biochemists to further examine the relationship between three- 

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Martin YC, Bures MG, Willett P. Searching databases of three-dimensional structures. In Lipkowitz KB, Boyd DB, editors. Reviews in Computational Chemistry, Vol. 1. New York VCH, 1990. p. 213-63. 

Y. C. Martin, M. G. Bures, and P. Willett, this volume. Searching Databases of Three-Dimensional Structures. 

Martin, Y.C. Bures, M.G. Willett, P. Searching Databases of Three-dimensional Structures. In Reviews in Computational Chemistry Lipkowitt, K.B. Boyd. D.B., Eds., VCH New York, 1990. 

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