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Molecular Similarity in Drug Design pp 24–56Cite as

3D molecular similarity indices and their application in QSAR studies

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Abstract

In order to undertake 3D QSAR calculations or database searches for a biomolecular system of interest, the creation of some form of binding mode model is essential. It is often the case that while a number of ligands for a given receptor are known, the receptor structure itself is not. In this instance, one must infer the critical interactions from ligand structure. While the use of atom—atom matches between ligands are frequently used to this end, such a correspondence is not always obvious when bonding topologies show significant divergence. The two molecules rolipram and denbufylline Figure 2.1 provide a good illustration of this. While both compounds are inhibitors of phosphodiesterase, their structures show no simple atom—atom correspondence. In these circumstances the search for complementarity in molecular properties such as molecular electrostatic potential (MEP) and shape provides an attractive alternative for determining potential pharmacophores. 3D molecular similty indices provide an efficient way by which these comparisons may be undertaken. A 3D molecular similarity index is essentially a mathematical function of the molecular properties it is used to compare. By overlaying two molecules and applying the index over property space, a numerical value for the molecular similarity is determined. The numbers obtained from molecular similarity calculations contain much information regarding the quantitative relationships between ligand properties.

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  1. A. C. Good
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  1. Department of Pharmacology, University of Cambridge, Cambridge, UK

    P. M. Dean

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Good, A.C. (1995). 3D molecular similarity indices and their application in QSAR studies. In: Dean, P.M. (eds) Molecular Similarity in Drug Design. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-1350-2_2

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  • DOI: https://doi.org/10.1007/978-94-011-1350-2_2

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