GLYCAM06: A generalizable biomolecular force field. Carbohydrates

TLDR

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. A new derivation of the GLYCAM06 force field that removes its previous specificity for carbohydrates and its dependency on the AMBER force field and parameters is presented. All pertinent force field terms are explicitly specified, with torsion terms derived from quantum mechanical data on minimal molecular fragments and related small molecules, eliminating default or generic parameters. GLYCAM06 now provides a single parameter set for all carbohydrate anomers and ring sizes, and by fitting dihedral terms to quantum mechanical rotational energy curves it reproduces correct rotamer populations in both gas‑phase and condensed‑phase simulations, though some cases remain challenging, while also reproducing crystalline lattice properties and vibrational frequencies. © 2007 Wiley Periodicals, Inc., J Comput Chem, 2008.

Abstract

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