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Open Access Highly Accessed Research article

Calculated conformer energies for organic molecules with multiple polar functionalities are method dependent: Taxol (case study)

Ami Lakdawala1, Minmin Wang1, Neysa Nevins1, Dennis C Liotta1, Danuta Rusinska-Roszak2, Marek Lozynski2 and James P Snyder1*

Author Affiliations

1 Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA

2 Department of Chemical Technology, Poznan University of Technology, 60-965 Poznan, Poland

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BMC Chemical Biology 2001, 1:2  doi:10.1186/1472-6769-1-2

Published: 1 October 2001

Abstract

Background

Molecular mechanics (MM) and quantum chemical (QM) calculations are widely applied and powerful tools for the stereochemical and conformational investigations of molecules. The same methods have been extensively used to probe the conformational profile of Taxol (Figure 1) both in solution and at the β-tubulin protein binding site.

Results

In the present work, the relative energies of seven conformations of Taxol derived from NMR and X-ray analyses were compared with a set of widely used force fields and semiempirical MO methods coupled to a continuum solvent treatment. The procedures not only diverge significantly in their assessment of relative conformational energies, but none of them provide satisfactory agreement with experiment.

Conclusions

For Taxol, molecular mechanics and semiempirical QM methods are unable to provide a consistent energetic ranking of side-chain conformations. For similar highly polar organic structures, "energy-free" conformational search methods are advised.