Assessing the performance of computational methods for the prediction of the ground state structure of a cyclic decapeptide

Authors

  • Manuel Doemer,

    1. Laboratoire de Chimie et Biochimie Computationelle, Institut des Sciences et Ingénierie Chimique, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
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  • Matteo Guglielmi,

    1. Laboratoire de Chimie et Biochimie Computationelle, Institut des Sciences et Ingénierie Chimique, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
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  • Prashanth Athri,

    1. Laboratoire de Chimie et Biochimie Computationelle, Institut des Sciences et Ingénierie Chimique, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
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  • Natalia S. Nagornova,

    1. Laboratoire de Chimie Physique Moléculaire, Institut des Sciences et Ingénierie Chimique, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
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  • Thomas R. Rizzo,

    1. Laboratoire de Chimie Physique Moléculaire, Institut des Sciences et Ingénierie Chimique, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
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  • Oleg V. Boyarkin,

    1. Laboratoire de Chimie Physique Moléculaire, Institut des Sciences et Ingénierie Chimique, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
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  • Ivano Tavernelli,

    1. Laboratoire de Chimie et Biochimie Computationelle, Institut des Sciences et Ingénierie Chimique, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
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  • Ursula Rothlisberger

    Corresponding author
    1. Laboratoire de Chimie et Biochimie Computationelle, Institut des Sciences et Ingénierie Chimique, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
    • Laboratoire de Chimie et Biochimie Computationelle, Institut des Sciences et Ingénierie Chimique, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
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Abstract

We benchmark the performance of various computational approaches, ranging from the classical nonpolarizable force fields AMBER FF96 and FF99SB, the polarizable force fields AMBER FF02polEP and AMOEBAbio09 to the semiempirical DFT method SCC-DFTB. The test set consists of nine conformations of gas-phase protonated gramicidin S, a cyclic decapeptide. We discuss their structural features in relation to the intrinsic lowest energy structure, which has been solved recently by a combination of cold ion spectroscopy and high level theoretical methods (Nagornova et al., Angew Chem Int Ed 2011, 50, 5383). As a reference, we use the energetics at the M05-2X level of theory. The latter has been validated as a suitable reference method in predicting the correct ground state structure of gas-phase protonated bare and microsolvated tryptophan as well as gas-phase protonated gramicidin S by comparison to experiment. We discuss the performance of the different more approximate methods in relation to their potential use as efficient and reliable tools to explore conformational space for the generation of candidate structures before refinement at the DFT level. © 2012 Wiley Periodicals, Inc.

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