3-D pharmacophores in drug discovery.
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.
Mason
J S
JS
Structural Biology and Modeling, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ 08543, USA. JONATHAN.MASON@BMS.COM
Good
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AC
Martin
E J
EJ
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding