Searching for pharmacophoric patterns in databases of three-dimensional chemical structures.
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.
Willett
P
P
Krebs Institute for Biomolecular Research, University of Sheffield, UK.
D000465:Algorithms; D016208:Databases, Factual; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure