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The great descriptor melting pot: mixing descriptors for the common good of QSAR models

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Abstract

The usefulness and utility of QSAR modeling depends heavily on the ability to estimate the values of molecular descriptors relevant to the endpoints of interest followed by an optimized selection of descriptors to form the best QSAR models from a representative set of the endpoints of interest. The performance of a QSAR model is directly related to its molecular descriptors. QSAR modeling, specifically model construction and optimization, has benefited from its ability to borrow from other unrelated fields, yet the molecular descriptors that form QSAR models have remained basically unchanged in both form and preferred usage. There are many types of endpoints that require multiple classes of descriptors (descriptors that encode 1D through multi-dimensional, 4D and above, content) needed to most fully capture the molecular features and interactions that contribute to the endpoint. The advantages of QSAR models constructed from multiple, and different, descriptor classes have been demonstrated in the exploration of markedly different, and principally biological systems and endpoints. Multiple examples of such QSAR applications using different descriptor sets are described and that examined. The take-home-message is that a major part of the future of QSAR analysis, and its application to modeling biological potency, ADME-Tox properties, general use in virtual screening applications, as well as its expanding use into new fields for building QSPR models, lies in developing strategies that combine and use 1D through nD molecular descriptors.

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Authors and Affiliations

  1. Department of Computer Science and Information Engineering, National Taiwan University, No. 1 Sec. 4, Roosevelt Road, Taipei, 106, Taiwan

    Yufeng J. Tseng

  2. Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No. 1 Sec. 4, Roosevelt Road, Taipei, 106, Taiwan

    Yufeng J. Tseng

  3. College of Pharmacy MSC09 5360 1, University of New Mexico, Albuquerque, NM, 87131-0001, USA

    Anton J. Hopfinger

  4. The Chem21 Group, Inc., 1780 Wilson Drive, Lake Forest, IL, 60045, USA

    Anton J. Hopfinger & Emilio Xavier Esposito

  5. exeResearch, LLC, 32 University Drive, East Lansing, MI, 48823, USA

    Emilio Xavier Esposito

Authors
  1. Yufeng J. Tseng
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  2. Anton J. Hopfinger
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  3. Emilio Xavier Esposito
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Correspondence to Emilio Xavier Esposito.

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Tseng, Y.J., Hopfinger, A.J. & Esposito, E.X. The great descriptor melting pot: mixing descriptors for the common good of QSAR models. J Comput Aided Mol Des 26, 39–43 (2012). https://doi.org/10.1007/s10822-011-9511-4

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  • DOI: https://doi.org/10.1007/s10822-011-9511-4

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