Solvation properties ofN‐acetyl‐β‐glucosamine: Molecular dynamics study incorporating electrostatic polarization

Abstract

N-acetyl-β-glucosamine (NAG) is an important moiety of glycoproteins and is involved in many biological functions. However, conformational and dynamical properties of NAG molecules in aqueous solution, the most common biological environment, remain ambiguous due to limitations of experimental methods. Increasing efforts are made to probe structural properties of NAG and NAG-containing macromolecules, like peptidoglycans and polymeric chitin, at the atomic level using molecular dynamics simulations. In this work, we develop a polarizable carbohydrate force field for NAG and contrast simulation results of various properties using this novel force field and an analogous non-polarizable (fixed charge) model. Aqueous solutions of NAG and its oligomers are investigated; we explore conformational properties (rotatable bond geometry), electrostatic properties (dipole moment distribution), dynamical properties (self-diffusion coefficient), hydrogen bonding (water bridge structure and dynamics), and free energy of hydration. The fixed-charge carbohydrate force field exhibits deviations from the gas-phase relative rotation energy of exocyclic hydroxymethyl side-chain and of chair/boat ring distortion. The polarizable force field predicts conformational properties in agreement with corresponding first-principles results. NAG-water hydrogen bonding pattern is studied through radial distribution functions and correlation functions. Intermolecular hydrogen bonding between solute and solvent is found to stabilize NAG solution structures while intramolecular hydrogen bonds define glycosidic linkage geometry of NAG oligomers. The electrostatic component of hydration free energy is highly dependent on force field atomic partial charges, influencing a more favorable free energy of hydration in the fixed-charge model compared to the polarizable model.

Binding structures of tri‐N‐acetyl‐β‐glucosamine in hen egg white lysozyme using molecular dynamics with a polarizable force field

“…Recently, we developed a polarizable force field for NAG molecule and compared with an existing fixed‐charge force field (see Ref. [22]). Here, we apply the polarizable (nonadditive electrostatic) model along with a polarizable protein force field[23, 24] to study the binding structure of HEWL–(NAG) 3 .…”

Recent applications and developments of charge equilibration force fields for modeling dynamical charges in classical molecular dynamics simulations

“…Our work in the past several years has slowly demonstrated the utility of polarizable force fields, particularly those based on the charge equilibration formalism, for a broad range of physical and biophysical systems. We have constructed polarizable force fields for small molecules [36, 42-44, 125, 136, 137], proteins [37], lipids, and lipid bilayers [43,86,[138][139][140] and recently have begun work on carbohydrate force fields [125]. The latter area has been relatively untouched by force field developers with particular focus on polarizable, non-additive interaction potential models.…”

“…We used the CHEQ force field for proteins [36], water [31], and NAG 3 [125]. The simulations are the initial steps towards application of our models for protein-ligand absolute and relative binding free energy calculations using statistical mechanical approaches such as thermodynamic integration.…”

Dependence of enthalpic pairwise self-interactions on ionic strength: Some 2-deoxy and N-acetyl monosaccharides in aqueous NaCl solutions at T=298.15K

“…Theoretical and experimental study concerning the thermodynamic properties of monosaccharides and analogues in aqueous solutions that contain various co-solute or co-solvent molecules of biological interest is a lasting hot spot in biophysical chemistry [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Most of the phyiso-chemical investigations on molecular interactions of them with other compounds in aqueous solutions were carried out by the methods of calorimetry [23][24][25], densimetry and sound velocity [26,27], ultrafast spectroscopy [28], size-exclusion chromatography (SEC) and differential viscometry (VISC) [29], FTIR and Raman spectroscopies [30], NMR and simulation [31], as well as by combinatorial methods of thermodynamics [32].…”

“…These studies are very helpful to gain insight into intermolecular bonding and non-bonding interactions of different characteristics in solutions containing this kind of small biological compounds and other organic or inorganic molecules. However, little information can be found as yet about the thermodynamics of molecular interactions and other molecular properties of deoxy-and N-acetyl monosaccharides in aqueous solutions [17,[40][41][42][43][44].…”