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Representation of molecular structure using quantum topology with inductive logic programming in structure–activity relationships

Journal of Computer-Aided Molecular Design volume 20, pages 361–373 (2006)Cite this article

Abstract

The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader’s quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity.

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Notes

  1. King et al. [6] wrongly classified one of the inactive compounds as active resulting in 13 active compounds. This explains the higher accuracy reported here.

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Acknowledgement

This work was supported by The Norwegian Research Council (grant no. 154265/V40).

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Affiliations

  1. Chemometrics and Bioinformatics Group, Department of chemistry, Norwegian University of Science and Technology, Trondheim, Norway

    Bård Buttingsrud, Einar Ryeng & Bjørn K. Alsberg

  2. Computational Biology Group, Department of Computer Science, University of Wales Aberystwyth, Wales, United Kingdom

    Ross D. King

Authors
  1. Bård Buttingsrud
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  2. Einar Ryeng
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  3. Ross D. King
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  4. Bjørn K. Alsberg
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Correspondence to Bjørn K. Alsberg.

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Buttingsrud, B., Ryeng, E., King, R.D. et al. Representation of molecular structure using quantum topology with inductive logic programming in structure–activity relationships. J Comput Aided Mol Des 20, 361–373 (2006). https://doi.org/10.1007/s10822-006-9058-y

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  • DOI: https://doi.org/10.1007/s10822-006-9058-y

Keywords

  • Structure representation using quantum topology (StruQT)
  • Atoms in molecules (AIM)
  • Bader theory
  • Inductive logic programming (ILP)
  • Structure–activity relationship (SAR)
  • Quantitative structure–activity relationship (QSAR)