Journal of Computer-Aided Molecular Design

, Volume 22, Issue 12, pp 857–871 | Cite as

On the interpretation and interpretability of quantitative structure–activity relationship models

  • Rajarshi Guha


The goal of a quantitative structure–activity relationship (QSAR) model is to encode the relationship between molecular structure and biological activity or physical property. Based on this encoding, such models can be used for predictive purposes. Assuming the use of relevant and meaningful descriptors, and a statistically significant model, extraction of the encoded structure–activity relationships (SARs) can provide insight into what makes a molecule active or inactive. Such analyses by QSAR models are useful in a number of scenarios, such as suggesting structural modifications to enhance activity, explanation of outliers and exploratory analysis of novel SARs. In this paper we discuss the need for interpretation and an overview of the factors that affect interpretability of QSAR models. We then describe interpretation protocols for different types of models, highlighting the different types of interpretations, ranging from very broad, global, trends to very specific, case-by-case, descriptions of the SAR, using examples from the training set. Finally, we discuss a number of case studies where workers have provide some form of interpretation of a QSAR model.


Quantitative structure–activity relationship (QSAR) Interpretation Linear regression Partial least squares (PLS) Neural network 



I would like to thank Prof. Gerald Maggiora and Dr. David Stanton for useful comments on the issues underlying interpretability.


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© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.School of InformaticsIndiana UniversityBloomingtonUSA

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