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Application of QSAR and Shape Pharmacophore Modeling Approaches for Targeted Chemical Library Design

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Chemical Library Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 685))

Abstract

Optimization of chemical library composition affords more efficient identification of hits from biological screening experiments. The optimization could be achieved through rational selection of reagents used in combinatorial library synthesis. However, with a rapid advent of parallel synthesis methods and availability of millions of compounds synthesized by many vendors, it may be more efficient to design targeted libraries by means of virtual screening of commercial compound collections. This chapter reviews the application of advanced cheminformatics approaches such as quantitative structure–activity relationships (QSAR) and pharmacophore modeling (both ligand and structure based) for virtual screening. Both approaches rely on empirical SAR data to build models; thus, the emphasis is placed on achieving models of the highest rigor and external predictive power. We present several examples of successful applications of both approaches for virtual screening to illustrate their utility. We suggest that the expert use of both QSAR and pharmacophore models, either independently or in combination, enables users to achieve targeted libraries enriched with experimentally confirmed hit compounds.

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Acknowledgments

AT acknowledges the support from NIH (grant R01GM066940). J.E. and W.Z. acknowledge the financial support by the Golden Leaf Foundation via the BRITE Institute, North Carolina Central University. W.Z. also acknowledges funding from NIH (grant SC3GM086265).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, BRITE Institute, North Carolina Center University, Durham, NC, USA

    Jerry O. Ebalunode & Weifan Zheng

  2. Laboratory for Molecular Modeling and Carolina Center for Exploratory Cheminformatics Research, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Alexander Tropsha

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  1. Jerry O. Ebalunode
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  2. Weifan Zheng
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  3. Alexander Tropsha
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Correspondence to Jerry O. Ebalunode .

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  1. , Department of Pharmacology, University of California, La Jolla, 92093, California, USA

    Joe Zhongxiang Zhou

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Ebalunode, J.O., Zheng, W., Tropsha, A. (2011). Application of QSAR and Shape Pharmacophore Modeling Approaches for Targeted Chemical Library Design. In: Zhou, J. (eds) Chemical Library Design. Methods in Molecular Biology, vol 685. Humana Press. https://doi.org/10.1007/978-1-60761-931-4_6

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  • DOI: https://doi.org/10.1007/978-1-60761-931-4_6

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