Searching for pharmacophoric patterns in databases of three‐dimensional chemical structures

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Abstract
This paper provides an overview of the research that has been carried out in Sheffield over the last decade into searching techniques for databases of three‐dimensional (3D) chemical structures. A 3D structure or query pattern is represented by a labelled graph, in which the nodes and the edges of the graph are used to represent atoms and the associated inter‐atomic distances, respectively. The presence of a pharmacophore in each of the structures in a database can then be tested by means of a subgraph isomorphism algorithm, the computational requirements of which are minimized by the use of an initial screening procedure that eliminates the majority of the structures from the subgraph‐isomorphism search. Analogous graph‐based representation and searching methods can also be used with flexible 3D structures: in this case, the edges of the graphs represent inter‐atomic distance ranges and a final conformational search needs to be carried out for those molecules that match the query pharmacophore in the subgraph‐isomorphism search. The paper also reviews related work on the automatic identification of pharmacophoric patterns and on 3D similarity searching.