GLYCAM06: A generalizable biomolecular force field. Carbohydrates

Authors

  • Karl N. Kirschner,

    1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602
    Current affiliation:
    1. Center for Molecular Design, Hamilton College, Clinton, New York 13323
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    • The first two authors contributed equally to this work

  • Austin B. Yongye,

    1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602
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    • Sarah M. Tschampel,

      1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602
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    • Jorge González-Outeiriño,

      1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602
      Current affiliation:
      1. Information Technology and Services, Syracuse University, 250 Machinery Hall Syracuse, NY 13244
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    • Charlisa R. Daniels,

      1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602
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    • B. Lachele Foley,

      1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602
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    • Robert J. Woods

      Corresponding author
      1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602
      • Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, Georgia 30602
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    Abstract

    A new derivation of the GLYCAM06 force field, which removes its previous specificity for carbohydrates, and its dependency on the AMBER force field and parameters, is presented. All pertinent force field terms have been explicitly specified and so no default or generic parameters are employed. The new GLYCAM is no longer limited to any particular class of biomolecules, but is extendible to all molecular classes in the spirit of a small-molecule force field. The torsion terms in the present work were all derived from quantum mechanical data from a collection of minimal molecular fragments and related small molecules. For carbohydrates, there is now a single parameter set applicable to both α- and β-anomers and to all monosaccharide ring sizes and conformations. We demonstrate that deriving dihedral parameters by fitting to QM data for internal rotational energy curves for representative small molecules generally leads to correct rotamer populations in molecular dynamics simulations, and that this approach removes the need for phase corrections in the dihedral terms. However, we note that there are cases where this approach is inadequate. Reported here are the basic components of the new force field as well as an illustration of its extension to carbohydrates. In addition to reproducing the gas-phase properties of an array of small test molecules, condensed-phase simulations employing GLYCAM06 are shown to reproduce rotamer populations for key small molecules and representative biopolymer building blocks in explicit water, as well as crystalline lattice properties, such as unit cell dimensions, and vibrational frequencies. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008

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