Current Pharmaceutical Design

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3-D Pharmacophores in Drug Discovery

Author(s): J. S. Mason, A. C. Good and E. J. Martin

Affiliation: Structural Biology and Modeling, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ 08543, USA.

Abstract:

In this chapter we review the use of 3-D pharmacophores in drug discovery. Recent advances are highlighted, including the application of pharmacophore descriptors generated both from ligands and protein binding sites. The application of 3-D pharmacophore fingerprints as molecular descriptors for similarity and diversity applications such as virtual screening, library design and QSAR is discussed . In addition, we highlight the quantification of structure-based diversity using site-derived fingerprints, and review virtual screening methods using both single refined hypotheses and the fingerprints of multiple potential hypotheses. Further, we discuss methods that take protein flexibility and molecular shape-into account. Each of the above techniques are reviewed with particular reference to the recent advances, advantages and challenges of each methodology.

Keywords: Pharmacophores in Drug Discovery, hydrogen bond donors, Prediction of ADME, ChemDiverse, potential tautomerism, DiR query, GRID analyses, Daichii factor, Hopkins statistic, MDDR ER active molecules

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Article Details

VOLUME: 7
ISSUE: 7
Page: [567 - 597]
Pages: 31
DOI: 10.2174/1381612013397843