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3-D Pharmacophores in Drug Discovery

[ Vol. 7 , Issue. 7 ]

Author(s):

J. S. Mason, A. C. Good and E. J. Martin   Pages 567 - 597 ( 31 )

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

Affiliation:

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



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