BCL::EMAS — Enantioselective Molecular Asymmetry Descriptor for 3D-QSAR
Department of Chemistry, Pharmacology, and Biomedical Informatics, Center for Structural Biology, Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232-6600, USA
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Molecules 2012, 17(8), 9971-9989; https://doi.org/10.3390/molecules17089971
Received: 29 June 2012
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Revised: 15 August 2012
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Accepted: 15 August 2012
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Published: 20 August 2012
(This article belongs to the Special Issue QSAR and Its Applications)
Stereochemistry is an important determinant of a molecule’s biological activity. Stereoisomers can have different degrees of efficacy or even opposing effects when interacting with a target protein. Stereochemistry is a molecular property difficult to represent in 2D-QSAR as it is an inherently three-dimensional phenomenon. A major drawback of most proposed descriptors for 3D-QSAR that encode stereochemistry is that they require a heuristic for defining all stereocenters and rank-ordering its substituents. Here we propose a novel 3D-QSAR descriptor termed Enantioselective Molecular ASymmetry (EMAS) that is capable of distinguishing between enantiomers in the absence of such heuristics. The descriptor aims to measure the deviation from an overall symmetric shape of the molecule. A radial-distribution function (RDF) determines a signed volume of tetrahedrons of all triplets of atoms and the molecule center. The descriptor can be enriched with atom-centric properties such as partial charge. This descriptor showed good predictability when tested with a dataset of thirty-one steroids commonly used to benchmark stereochemistry descriptors (r2 = 0.89, q2 = 0.78). Additionally, EMAS improved enrichment of 4.38 versus 3.94 without EMAS in a simulated virtual high-throughput screening (vHTS) for inhibitors and substrates of cytochrome P450 (PUBCHEM AID891).
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Keywords:
QSAR; CADD; stereochemistry; enantiomer; molecular asymmetry; chirality
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MDPI and ACS Style
Sliwoski, G.; Lowe, E.W., Jr.; Butkiewicz, M.; Meiler, J. BCL::EMAS — Enantioselective Molecular Asymmetry Descriptor for 3D-QSAR. Molecules 2012, 17, 9971-9989. https://doi.org/10.3390/molecules17089971
AMA Style
Sliwoski G, Lowe EW Jr., Butkiewicz M, Meiler J. BCL::EMAS — Enantioselective Molecular Asymmetry Descriptor for 3D-QSAR. Molecules. 2012; 17(8):9971-9989. https://doi.org/10.3390/molecules17089971
Chicago/Turabian StyleSliwoski, Gregory, Edward W. Lowe Jr., Mariusz Butkiewicz, and Jens Meiler. 2012. "BCL::EMAS — Enantioselective Molecular Asymmetry Descriptor for 3D-QSAR" Molecules 17, no. 8: 9971-9989. https://doi.org/10.3390/molecules17089971
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