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Building a Quantitative Structure-Property Relationship (QSPR) Model

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Bioinformatics and Drug Discovery

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1939))

Abstract

Knowing the physicochemical and general biochemical properties of a compound is critical to understanding how it behaves in different biological environments and to anticipating what is likely to happen in situations where that behavior cannot be measured directly. Quantitative structure-property relationship (QSPR) models provide a way to predict those properties even before a compound has been synthesized simply by knowing what its structure would be. This chapter describes a general workflow for compiling the data upon which a useful QSPR model is built, curating it, evaluating that model’s performance, and then analyzing the predictive errors with an eye toward identifying systematic errors in the input data. The focus here is on models for the absorption, distribution, metabolism, and excretion (ADME) properties of drugs and toxins, but the considerations explored are general and applicable to any QSPR.

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Notes

  1. 1.

    Chemical structures can also be extracted from text documents by applying optical structure recognition (OSR). Those that the authors have worked with are not yet reliable enough to be applied without careful manual review.

  2. 2.

    Bridging hydrogen atoms that take part in three-center bonds are treated as part of the core structure.

  3. 3.

    Where necessary, promising groups of descriptors are generated using a genetic algorithm (GA) [28].

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Acknowledgments

The authors would like to acknowledge Michael S. Lawless, Marvin Waldman, and Walter S. Woltosz of Simulations Plus, Inc., for their careful reading of the manuscript and their insightful suggestions.

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Authors and Affiliations

  1. Simulations Plus, Inc., Lancaster, CA, USA

    Robert D. Clark & Pankaj R. Daga

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  1. Robert D. Clark
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  2. Pankaj R. Daga
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Corresponding author

Correspondence to Robert D. Clark .

Editor information

Editors and Affiliations

  1. Department of Pathology, University of New Mexico, Albuquerque, NM, USA

    Richard S. Larson

  2. Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA

    Tudor I. Oprea

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Clark, R.D., Daga, P.R. (2019). Building a Quantitative Structure-Property Relationship (QSPR) Model. In: Larson, R., Oprea, T. (eds) Bioinformatics and Drug Discovery. Methods in Molecular Biology, vol 1939. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9089-4_8

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  • DOI: https://doi.org/10.1007/978-1-4939-9089-4_8

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9088-7

  • Online ISBN: 978-1-4939-9089-4

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