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. 2019 Sep 10;15(9):4982-5000.
doi: 10.1021/acs.jctc.9b00327. Epub 2019 Aug 29.

Drude Polarizable Force Field Parametrization of Carboxylate and N-Acetyl Amine Carbohydrate Derivatives

Poonam Pandey, Asaminew H Aytenfisu  1 , Alexander D MacKerell Jr  1 , Sairam S Mallajosyula
Affiliations

Drude Polarizable Force Field Parametrization of Carboxylate and N-Acetyl Amine Carbohydrate Derivatives

Poonam Pandey et al. J Chem Theory Comput. .

Abstract

In this work, we report the development of Drude polarizable force field parameters for the carboxylate and N-acetyl amine derivatives, extending the functionality of the existing Drude polarizable carbohydrate force field. The force field parameters have been developed in a hierarchical manner, reproducing the quantum mechanical gas-phase properties of small model compounds representing the key functional group in the carbohydrate derivatives, including optimization of the electrostatic and bonded parameters. The optimized parameters were then used to generate the models for carboxylate and N-acetyl amine carbohydrate derivatives. The transferred parameters were further tested and optimized to reproduce crystal geometries and J-coupling data from nuclear magnetic resonance experiments. The parameter development resulted in the incorporation of d-glucuronate, l-iduronate, N-acetyl-d-glucosamine (GlcNAc), and N-acetyl-d-galactosamine (GalNAc) sugars into the Drude polarizable force field. The parameters developed in this study were then applied to study the conformational properties of glycosaminoglycan polymer hyaluronan, composed of d-glucuronate and N-acetyl-d-glucosamine, in aqueous solution. Upon comparing the results from the additive and polarizable simulations, it was found that the inclusion of polarization improved the description of the electrostatic interactions observed in hyaluronan, resulting in enhanced conformational flexibility. The developed Drude polarizable force field parameters in conjunction with the remainder of the Drude polarizable force field parameters can be used for future studies involving carbohydrates and their conjugates in complex, heterogeneous systems.

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Figures

Figure 1.
Figure 1.
Schematic representation of Drude oscillator model for carbonyl functional (C=O) group. (a) The carbon and oxygen atoms are represented as sphere with the partially positively charged nucleus and partially negatively charged Drude particle. (b) Orientation of the Drude particle in the influence of electrical field, E, parallel and perpendicular to the interatomic covalent bond.
Figure 2.
Figure 2.
Schematic illustration of (a) interconversion of 1C4 chair to 4C1 configuration in Iduronate, (b) preferential occurrence of 4C1 configuration in Glucuronate. (all schematic diagrams were prepared with ChemBioDraw Ultra 13.0)
Figure 3.
Figure 3.
Model compounds used to develop parameters for carbohydrate derivatives (a) M1 (2- methoxy propionate): for glucuronate and iduronate, and (b) M2 (N-isopropyl acetamide): for GlcNAc and GalNAc. (all schematic diagrams were prepared with ChemBioDraw Ultra 13.0)
Figure 4.
Figure 4.
Chemical structures of glucopyranose derivatives (a) D-glucuronate, (b) L-iduronate, (c) N-acetyl-D-glucosamine (GlcNAc) and (d) N-acetyl-D-galactosamine (GalNAc). (all schematic diagrams were prepared with ChemBioDraw Ultra 13.0)
Figure 5.
Figure 5.
Relaxed potential energy scans of O5-C5-C6-O61 dihedral in compound M1.
Figure 6.
Figure 6.
Monohydrate water interaction geometries with model compound M1. Interactions (a) and (b) have the M1 C6-O61 and C5-C6 bonds collinear with the water HO bond, respectively, and with the water molecule in the same plane as the carboxyl group; interactions (c) and (d) have the water HO bond collinear with the ether C1-O5-C5 angle bisector and with the water molecule in the same plane as the C1-O5-C5 atoms; and interactions (e) and (f) have the water molecule forming a tetrahedral interaction with the ether and with the water molecule perpendicular to the plane of the C1-O5-C5 atoms. All molecular graphics were prepared with VMD.
Figure 7.
Figure 7.
1D dihedral potential energy scans about O61-C6-C5-O5 dihedrals for α-/β- Glucuronate (a, b, c and d), and α-/β- Iduronate (e, f, g and h). Only those conformers with relative energies < 20 kcal/mol are included in the figure.
Figure 8.
Figure 8.
Water pair interaction geometries with acidic sugars. Interactions (a) and (b) have the water HO bond collinear with the C5-O5-C1 angle bisector, with the water molecule in the same plane as the C5-O5-C1 atoms; interactions (c) and (d) have the water molecule forming a tetrahedral interaction with the O5, with the water molecule perpendicular to the plane of the C5-O5-C1 atoms; interactions (e) and (f) have the water HO bond collinear with the C5-O5-C1 angle bisector, with the water molecule perpendicular to the plane of the C5-O5-C1 atoms; and interaction (g) has the C5-H5 vector collinear with the water HOH angle bisector. (All molecular graphics were prepared with VMD)
Figure 9.
Figure 9.
Relaxed potential energy scans of the C-N-C2-C3 dihedral in compound M2.
Figure 10.
Figure 10.
Water pair interaction geometries with model compound M2. Interactions (a) and (b) have the NH vector collinear with water HOH angle bisector; in (a) the water molecule is coplanar with the amide group and in (b) the water molecule is perpendicular. Interaction (c) has the CO vector collinear with the water HO vector and interaction (d) has these two vectors forming a 120°angle; in both (c) and (d) water molecule is coplanar with the amide group. (All molecular graphics were prepared with VMD)
Figure 11.
Figure 11.
1D dihedral potential energy scans about C-N-C2-C1 dihedrals for α-/β- N-acetyl-D-glucosamine (a and b), and N-acetyl-D-galactosamine (c and d).
Figure 12.
Figure 12.
Water pair interaction geometries with N-acetylamines (α-/β- GlcNAc and α-/β- GalNAc). Interaction (a) has the C1-H1 vector collinear with the water HOH angle bisector; and interaction (b) has the C2-H2 vector collinear with the water HOH angle bisector. All molecular graphics were prepared with VMD.
Figure 13.
Figure 13.
Conformational properties of the glycosidic linkages in unsulfated chondroitin (CN6). Figure (a) shows the crystal structure (PDB ID: 2KQO) of unsulfated chondroitin demonstrating β-D-glucuronate (1→3) β-N-acetyl galactosamines linkage and β-N-acetyl galactosamines (1→4) β-D-glucuronate linkage. The BGLCA and BGALNA units are represented as U and N, respectively. Boltzmann-inverted probability distribution of β (1→3)-glycosidic linkage (ϕ = O5(U)-C1(U)-O3(N)–C3(N) and ψ = C1(U)-O3(N)–C3(N)-C4(N)) is shown in Figure (b, c, d) and (e, f, g) for additive and Drude, respectively.
Figure 14.
Figure 14.
Boltzmann-inverted probability distribution of β (1→4)-glycosidic linkage (ϕ = O5(N)-C1(N)-O4(U)–C4(U) and ψ = C1(N)-O4(U)–C4(U)-C5(U)) in unsulfated chondroitin (CN6) is shown for additive (a and b) and Drude (c and d) simulations, respectively.
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References

    1. Kannagi R, Regulatory roles of carbohydrate ligands for selectins in the homing of lymphocytes. Curr Opin Struct Biol 2002, 12 (5), 599–608. - PubMed
    1. Bucior I; Burger MM, Carbohydrate–carbohydrate interactions in cell recognition. Curr Opin Struct Biol 2004, 14 (5), 631–637. - PubMed
    1. Lasky LA, Selectin-carbohydrate interactions and the initiation of the inflammatory response. Annu Rev Biochem 1995, 64 (1), 113–39. - PubMed
    1. Weis WI; Drickamer K, Structural basis of lectin-carbohydrate recognition. Annu Rev Biochem 1996, 65 (1), 441–73. - PubMed
    1. Lowe JB, Glycosylation, immunity, and autoimmunity. Cell 2001, 104 (6), 809–12. - PubMed

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