A reoptimized GROMOS force field for hexopyranose‐based carbohydrates accounting for the relative free energies of ring conformers, anomers, epimers, hydroxymethyl rotamers, and glycosidic linkage conformers

Abstract

This article presents a reoptimization of the GROMOS 53A6 force field for hexopyranose-based carbohydrates (nearly equivalent to 45A4 for pure carbohydrate systems) into a new version 56A(CARBO) (nearly equivalent to 53A6 for non-carbohydrate systems). This reoptimization was found necessary to repair a number of shortcomings of the 53A6 (45A4) parameter set and to extend the scope of the force field to properties that had not been included previously into the parameterization procedure. The new 56A(CARBO) force field is characterized by: (i) the formulation of systematic build-up rules for the automatic generation of force-field topologies over a large class of compounds including (but not restricted to) unfunctionalized polyhexopyranoses with arbritrary connectivities; (ii) the systematic use of enhanced sampling methods for inclusion of experimental thermodynamic data concerning slow or unphysical processes into the parameterization procedure; and (iii) an extensive validation against available experimental data in solution and, to a limited extent, theoretical (quantum-mechanical) data in the gas phase. At present, the 56A(CARBO) force field is restricted to compounds of the elements C, O, and H presenting single bonds only, no oxygen functions other than alcohol, ether, hemiacetal, or acetal, and no cyclic segments other than six-membered rings (separated by at least one intermediate atom). After calibration, this force field is shown to reproduce well the relative free energies of ring conformers, anomers, epimers, hydroxymethyl rotamers, and glycosidic linkage conformers. As a result, the 56A(CARBO) force field should be suitable for: (i) the characterization of the dynamics of pyranose ring conformational transitions (in simulations on the microsecond timescale); (ii) the investigation of systems where alternative ring conformations become significantly populated; (iii) the investigation of anomerization or epimerization in terms of free-energy differences; and (iv) the design of simulation approaches accelerating the anomerization process along an unphysical pathway.

Unique Aspects of the Structure and Dynamics of Elementary Iβ Cellulose Microfibrils Revealed by Computational Simulations

“…However, there is some evidence to suggest that the simulations presented here are sampling the correct exocyclic conformation for these solvent-exposed groups. Recent experimental data suggests that GT may be more populated than GG for Glc in solution (Hansen and Hünenberger, 2011). X-ray data for cellobiose has shown that the two exocyclic groups in the crystal structure adopt the GT conformation (Chu and Jeffrey, 1968).…”

On the anomalous temperature dependence of cellulose aqueous solubility

“…Aqueous cellotetraose was modeled using both the GROMOS 56 carbohydrate force field (Hansen and Hünenberger 2010) in combination with the SPC/E model (Berendsen et al 1987) for water, and the CHARMM C35 parameter set (Guvench et al 2008;Guvench et al 2009) together with TIP3P water (Jorgensen et al 1983). Water molecules were kept completely rigid using SETTLE (Miyamoto and Kollman 1992), and all covalent bonds in cellotetraose were kept at their equilibrium distances using P-LINCS (Hess 2008).…”

Amylose folding under the influence of lipids

“…8,9 Molecular dynamics (MD) simulations have proven to be a useful tool for providing a link between dynamics and structure. Many force fields have been extensively parameterized for carbohydrates, [10][11][12][13][14][15][16][17] and have been used to provide details of the structure and dynamics at an all atom (AA) level; for example to explore the ring puckering of glucose, 18,19 conformational changes in disaccharides and trisaccharides. 11,[20][21][22] However, previous MD studies of amylose have mainly dealt with small amylose fragments in water or studies of V-amylose in low polarity solvents.…”

“…46 to keep using them for the remainder of this work. Note that an improved GROMOS-based carbohydrate force field 19 has recently been released that might remedy some of the issues observed here.…”