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Template-based alignment modeling: an innovative ligand-based approach for medicinal chemists

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Abstract

A single protein-binding pocket often times binds to a diverse range of ligands with distinct structural features. Understanding the structural correlations of the different ligands remains a major challenge in medicinal chemistry research. We recently developed the template-based alignment modeling (TAM) method as a simple yet effective approach for understanding structure–activity relationships (SARs) for a variety of medicinal agents. In this article, we briefly review the developmental process of TAM, and then showcase some potential applications. Finally, within the conceptual framework of TAM, we discuss our view of the structural correlation issue of diverse ligands.

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Acknowledgements

This paper is dedicated to a special issue of Medicinal Chemistry Research in honoring Professor Hanzlik for his 49 years of teaching and research at the Department of Medicinal Chemistry, University of Kansas.

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Authors and Affiliations

  1. ABC Recourse, Plainsboro, NJ, 08536, USA

    Zhijun Wu

  2. Department of Chemistry and Chemical Biology, Rutgers, the State University of New Jersey, Piscataway, NJ, 08854, USA

    Spencer Knapp

  3. Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85716, USA

    Victor Hruby

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  1. Zhijun Wu
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  2. Spencer Knapp
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  3. Victor Hruby
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Correspondence to Zhijun Wu.

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Wu, Z., Knapp, S. & Hruby, V. Template-based alignment modeling: an innovative ligand-based approach for medicinal chemists. Med Chem Res 29, 1160–1167 (2020). https://doi.org/10.1007/s00044-020-02562-z

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