Next Article in Journal
Release of Terpenes from Fir Wood during Its Long-Term Use and in Thermal Treatment
Next Article in Special Issue
Computational Prediction of Blood-Brain Barrier Permeability Using Decision Tree Induction
Previous Article in Journal
Design and Synthesis of a Series of Pyrido[2,3-d]pyrimidine Derivatives as CCR4 Antagonists
Previous Article in Special Issue
Hologram QSAR Models of 4-[(Diethylamino)methyl]-phenol Inhibitors of Acetyl/Butyrylcholinesterase Enzymes as Potential Anti-Alzheimer Agents
Article Menu

Export Article

Open AccessArticle
Molecules 2012, 17(8), 9971-9989; doi:10.3390/molecules17089971

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
*
Author to whom correspondence should be addressed.
Received: 29 June 2012 / Revised: 15 August 2012 / Accepted: 15 August 2012 / Published: 20 August 2012
(This article belongs to the Special Issue QSAR and Its Applications)
View Full-Text   |   Download PDF [803 KB, uploaded 18 June 2014]   |  

Abstract

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). View Full-Text
Keywords: QSAR; CADD; stereochemistry; enantiomer; molecular asymmetry; chirality QSAR; CADD; stereochemistry; enantiomer; molecular asymmetry; chirality
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top