The application of molecular topology to drug design — topological descriptions of molecular shape

Abstract

Molecular similarity is becoming an increasingly important topic in drug design. Methods for determining similarity are required, for example, in order to compare the shapes, symmetries and electronic properties of molecules, or search databases for novel structures with features complementary to a biologically active ligand or a characterized receptor. Many of the procedures for assessing similarity are atom-based and use two- or three-dimensional geometry to superimpose or compare different molecular structures or conformations (Dean and Perkins, 1993; Richards, 1993). Because these methods involve calculations using very large sets of real numbers, they can prove inefficient when searching large databases for structures such as proteins which contain many atoms. If molecular flexibility is also considered, the computational problems can become intractable unless sensible approximations are employed (Dean and Perkins, 1993).