Interpretable correlation descriptors for quantitative structure-activity relationships.

Benson M Spowage,Jonathan D Hirst,Craig L Bruce

doi:10.1186/1758-2946-1-22

Benson M Spowage, Jonathan D Hirst + Show 1 more

Open Access

https://doi.org/10.1186/1758-2946-1-22

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Abstract

BackgroundThe 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.ResultsHere, 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1758-2946-1-22) contains supplementary material, which is available to authorized users.

Highlights

The topological maximum cross correlation (TMACC) descriptors are alignmentindependent 2D descriptors for the derivation of Quantitative structure-activity relationship (QSAR)
To exemplify the TMACC descriptors, we investigate two datasets, which were previously used in a comprehensive comparison of modern QSAR approaches [17]
Angiotensin converting enzyme (ACE) inhibition LOO cross-validation of the partial least squares (PLS) models generated for the angiotensin converting enzyme (ACE) and dihydrofolate reductase (DHFR) data sets gave q2 values of 0.70 and 0.53, respectively, consistent with those previously reported [9]

Summary

Results

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

Background

Results and Discussion

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Conclusion

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