Extension of the GROMOS 56a6_{CARBO/CARBO_R} Force Field for Charged, Protonated, and Esterified Uronates

Abstract

An extension of the GROMOS 56a6 force field for hexopyranose-based carbohydrates is presented. The additional parameters describe the conformational properties of uronate residues. The three distinct chemical states of the carboxyl group are considered: deprotonated (negatively charged), protonated (neutral), and esterified (neutral). The parametrization procedure was based on quantum-chemical calculations, and the resulting parameters were tested in the context of (i) flexibility of the pyranose rings under different pH conditions, (ii) conformation of the glycosidic linkage of the (1 → 4)-type for uronates with different chemical states of carboxyl moieties, (iii) conformation of the exocyclic (i.e., carboxylate and lactol) moieties, and (iv) structure of the Ca-linked chain-chain complexes of uronates. The presently proposed parameters in combination with the 56a6 set can be used to describe the naturally occurring polyuronates, composed either of homogeneous (e.g., glucuronans) or heterogeneous (e.g., pectins, alginates) segments. The results of simulations relying on the new set of parameters indicate that the conformation of glycosidic linkage is nearly unaffected by the chemical state of the carboxyl group, in contrary to the ring conformational equilibria. The calculations for the poly(α-d-galacturonate)-Ca and poly(α-l-guluronate)-Ca complexes show that both parallel and anitiparallel arrangements of uronate chains are possible but differ in several structural aspects.

Dissipative particle dynamics model of homogalacturonan based on molecular dynamics simulations

“…All MD simulations were carried out with the GROMACS 5.0 package 29 . The force field parameters used for the simulations were adopted from the GROMOS 56A6 CARBO force field 30 , 31 whereas the interactions involving carboxylate moieties were described in terms of the recently proposed extension of GROMOS 56A6 CARBO 22 . The molecular systems under consideration were placed in cubic simulation boxes filled with the appropriate number of simple point charge (SPC) water molecules 32 .…”

“…Some studies have also suggested that homogalacturonan can aggregate due to weak hydrogen bonding via carboxyl groups 17,18 . Until now, molecular studies of pectic polysaccharides have been limited to the interaction of two or three molecular chains with up to 20 residues [19][20][21][22][23] or conformations of single chains consisting of 50 residues 24 .…”

Three-Dimensional Structures of Carbohydrates and Where to Find Them

“…Another modification of 56A CARBO named 56A CARBO_CHT [ 189 ] was developed for chitosan and its derivatives. Recently, extensions of GROMOS 56A CARBO / CARBO_R parameter set were adapted towards charged, protonated and esterified urinates [ 190 ] and furanose-based carbohydrates [ 191 ]. GROMOS96 43A1 was reported to have good performance on glycan structure simulation in glycoproteins [ 192 , 193 ].…”

Structural Aspects of the O‐glycosylation Linkage in Glycopeptides via MD Simulations and Comparison with NMR Experiments

“…In this context, there is an ongoing effort in developing carbohydrate force fields within different force‐field families. Examples are CHARMM, GLYCAM06, GROMOS 53A6‐GLYC, GROMOS 56A6CARBO, MARTINI (coarse‐grained), and a recent polarazible DRUDE forcefield for carbohydrates . A review of some these force fields can be found in ref.…”