Research article

Interpretable correlation descriptors for quantitative structure-activity relationships

Benson M Spowage¹, Craig L Bruce^1,2 and Jonathan D Hirst^1*

• * Corresponding author: Jonathan D Hirst jonathan.hirst@nottingham.ac.uk

Author Affiliations

¹ School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK

² AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK

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Journal of Cheminformatics 2009, 1:22 doi:10.1186/1758-2946-1-22

Published: 24 December 2009

Abstract

Background

The topological maximum cross correlation (TMACC) descriptors are alignment-independent 2D descriptors for the derivation of QSARs. TMACC descriptors are generated using atomic properties determined by molecular topology. Previous validation (J Chem Inf Model 2007, 47: 626-634) of the TMACC descriptor suggests it is competitive with the current state of the art.

Results

Here, we illustrate the interpretability of the TMACC descriptors, through the analysis of the QSARs of inhibitors of angiotensin converting enzyme (ACE) and dihydrofolate reductase (DHFR). In the case of the ACE inhibitors, the TMACC interpretation shows features specific to C-domain inhibition, which have not been explicitly identified in previous QSAR studies.

Conclusions

The TMACC interpretation can provide new insight into the structure-activity relationships studied. Freely available, open source software for generating the TMACC descriptors can be downloaded from http://comp.chem.nottingham.ac.uk webcite.