Temperature Dependence of Hydroxymethyl Group Rotamer Populations in Cellooligomers

Empirical force fields for computer simulations of carbohydrates are often implicitly assumed to be valid also at temperatures different from room temperature for which they were optimized. Herein, the temperature dependence of the hydroxymethyl group rotamer populations in short oligosaccharides is investigated using molecular dynamics simulations and NMR spectroscopy. Two oligosaccharides, viz., methyl β-cellobioside and β-cellotetraose were simulated using three different carbohydrate force fields (CHARMM C35, GLYCAM06, and GROMOS 56Acarbo) in combination with different water models (SPC, SPC/E, and TIP3P) using replica exchange molecular dynamics simulations. For comparison, hydroxymethyl group rotamer populations were investigated for methyl β-cellobioside and cellopentaose based on measured NMR 3 J H5,H6 coupling constants, in the latter case by using a chemical shift selective NMR-filter. Molecular dynamics simulations in combination with NMR spectroscopy show that the temperature dependence of the hydroxymethyl rotamer population in these short cellooligomers, in the range 263–344 K, generally becomes exaggerated in simulations when compared to experimental data, but also that it is dependent on simulation conditions, and most notably properties of the water model.