Improved carbohydrate force field for gromos: ring and hydroxymethyl group conformations and exo-anomeric effect

A new GROMOS force field for hexopyranose‐based carbohydrates

“…However, for hexopyranoses of the D-series, the 43A1 and 45A3 force fields appear to overstabilize the 1 C 4 chair conformation relative to the (experimentally dominant, except for D-idopyranose 4 ) 4 C 1 conformation. This may result in undesired structural transitions between the two conformers, as previously reported in simulations using the 43A1 31,32,42,43 or 45A3 (unpublished results) parameter sets for carbohydrates. This problem was overcome by a slight modification of the scheme for the application of torsional potentials to sequences of ring atoms.…”

“…For this reason, it is often considered to be a challenging test for carbohydrate force fields. For example, incorrect rotameric distributions were observed in early versions of the CHARMM 17,19,83,84 and GROMOS 32,42 force fields, as well as in (comparatively shorter) Car-Parrinello simulations. 85 Taking into account the rather large uncertainty in the experimental estimates, the data reported in Table 6 indicate a very reasonable agreement with experiment.…”

“…The force field incorporating the two former modifications is referred to as the 45A3 force field. 37,38 However, simple tests using the GROMOS carbohydrate force field, either based on the original 43A1 parameter set 31,32,42,43 or on the 45A3 parameter set (unpublished data), have shown a strong underestimation of the anomeric effect and incorrect dihedral-angle distributions in simple di-and oligosaccharides, sometimes including distorted ring conformations. The required refinement of the GRO-MOS force field (mainly charges and torsional interaction parameters) in the context of hexopyranose-based carbohydrates is the goal of the present work.…”

Conformation, dynamics, solvation and relative stabilities of selected β-hexopyranoses in water: a molecular dynamics study with the gromos 45A4 force field

“…Due to their remarkable spatial (individual atoms) and temporal (femtosecond) resolution, as well as their firm basis in the laws of (classical) microscopic physics, explicit-solvent molecular dynamics (MD) simulations represent a key component in many theoretical approaches. A number of force fields have been developed to represent interatomic interactions in such simulations, which can be broadly classified into three categories: (i) force fields with the primary goal of reproducing properties in vacuum or together with an implicit representation of the solvent, for example, HSEA, 179 262 Spieser, 263 Galema 214,264 and 45A4 265,266 ); (iii) coarse-grained force fields with the primary goal of performing low-resolution simulations of large-scale systems or long timescale processes, for example, M3B. 267,268 For completeness, it should be mentioned that ab initio MD simulations of carbohydrates have also been performed.…”

“…The latter explicit-solvent simulations in the dilute regime were mostly concerned with (i) the validation and refinement of carbohydrate force field parameters; 239,243,[245][246][247][253][254][255][256][257][261][262][263]265,266 (ii) the investigation and rationalization of conformational properties 98,161,164,195,199,200,[214][215][216]239,241,243,[245][246][247]251,[253][254][255][256][257][261][262][263][264][265][266]269,277,278,[293][294][295][296]…”