Dataset Information

CHARMM Drude Polarizable Force Field for Glycosidic Linkages Involving Pyranoses and Furanoses.

ABSTRACT: We present an extension of the CHARMM Drude polarizable force field to enable modeling of polysaccharides containing pyranose and furanose monosaccharides. The new force field parameters encompass 1?2, 1?3, 1?4, and 1?6 pyranose-furanose linkages, 2?1 and 2?6 furanose-furanose linkages, 2?2, 2?3, and 2?4 furanose-pyranose, and 1?1, 1?2, 1?3, 1?4, and 1?6 pyranose-pyranose linkages. For the glycosidic linkages, both simple model compounds and the full disaccharides with methylation at the reducing end were used for parameter optimization. The model compounds were chosen to be monomers or glycosidic-linked dimers of tetrahydropyran (THP) and tetrahydrofuran (THF). Target data for optimization included one- and two-dimensional potential energy scans of ? and the ?/? glycosidic dihedral angles in the model compounds and full disaccharides computed by quantum mechanical (QM) RIMP2/cc-pVQZ single point energies on MP2/6-31G(d) optimized structures. Also included in the target data are extensive sets of QM gas phase monohydrate water-saccharide interactions, dipole moments, and molecular polarizabilities for both model compounds and full disaccharides. The resulting polarizable model is shown to be in good agreement with a range of QM data, offering a significant improvement over the additive CHARMM36 carbohydrate force field, as well as experimental data including crystal structures and conformational properties of disaccharides and a trisaccharide in aqueous solution.

SUBMITTER: Aytenfisu AH

PROVIDER: S-EPMC5997548 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

CHARMM Drude Polarizable Force Field for Glycosidic Linkages Involving Pyranoses and Furanoses.

Aytenfisu Asaminew H AH Yang Mingjun M MacKerell Alexander D AD

Journal of chemical theory and computation 20180504 6

We present an extension of the CHARMM Drude polarizable force field to enable modeling of polysaccharides containing pyranose and furanose monosaccharides. The new force field parameters encompass 1↔2, 1→3, 1→4, and 1→6 pyranose-furanose linkages, 2→1 and 2→6 furanose-furanose linkages, 2→2, 2→3, and 2→4 furanose-pyranose, and 1↔1, 1→2, 1→3, 1→4, and 1→6 pyranose-pyranose linkages. For the glycosidic linkages, both simple model compounds and the full disaccharides with methylation at the reducin ...[more]

PMID: 29694037

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Project description:We present an extension of the CHARMM hexopyranose monosaccharide additive all-atom force field to enable modeling of glycosidic-linked hexopyranose polysaccharides. The new force field parameters encompass 1→1, 1→2, 1→3, 1→4, and 1→6 hexopyranose glycosidic linkages, as well as O-methylation at the C(1) anomeric carbon, and are developed to be consistent with the CHARMM all-atom biomolecular force fields for proteins, nucleic acids, and lipids. The parameters are developed in a hierarchical fashion using model compounds containing the key atoms in the full carbohydrates, in particular O-methyl-tetrahydropyran and glycosidic-linked dimers consisting of two molecules of tetrahyropyran or one of tetrahydropyran and one of cyclohexane. Target data for parameter optimization include full two-dimensional energy surfaces defined by the Φ/Ψ glycosidic dihedral angles in the disaccharide analogs as determined by quantum mechanical MP2/cc-pVTZ single point energies on MP2/6-31G(d) optimized structures (MP2/cc-pVTZ//MP2/6-31G(d)). In order to achieve balanced, transferable dihedral parameters for the Φ/Ψ glycosidic dihedral angles, surfaces for all possible chiralities at the ring carbon atoms involved in the glycosidic linkages are considered, resulting in over 5000 MP2/cc-pVTZ//MP2/6-31G(d) conformational energies. Also included as target data are vibrational frequencies, pair interaction energies and distances with water molecules, and intramolecular geometries including distortion of the glycosidic valence angle as a function of the glycosidic dihedral angles. The model-compound optimized force field parameters are validated on full disaccharides through comparison of molecular dynamics results to available experimental data. Good agreement is achieved with experiment for a variety of properties including crystal cell parameters and intramolecular geometries, aqueous densities, and aqueous NMR coupling constants associated with the glycosidic linkage. The newly-developed parameters allow for the modeling of linear, branched, and cyclic hexopyranose glycosides both alone and in heterogenous systems including proteins, nucleic acids and/or lipids when combined with existing CHARMM biomolecular force fields.

Project description:A polarizable force field for nucleic acid bases based on the classical Drude oscillator model is presented. Parameter optimization was performed to reproduce crystallographic geometries, crystal unit cell parameters, heats of sublimation, vibrational frequencies and assignments, dipole moments, molecular polarizabilities and quantum mechanical base-base and base-water interaction energies. The training and validation data included crystals of unsubstituted and alkyl-substituted adenine, guanine, cytosine, uracil, and thymine bases, hydrated crystals, and hydrogen bonded base pairs. Across all compounds, the RMSD in the calculated heats of sublimation is 4.1%. This equates to an improvement of more than 2.5 kcal/mol in accuracy compared to the nonpolarizable CHARMM27 force field. However, the level of agreement with experimental molecular volume decreased from 1.7% to 2.1% upon moving from the nonpolarizable to the polarizable model. The representation of dipole moments is significantly improved with the Drude polarizable force field. Unlike in additive force fields, there is no requirement for the gas-phase dipole moments to be overestimated, illustrating the ability of the Drude polarizable force field to treat accurately differently dielectric environments and indicating the improvements in the electrostatic model. Validation of the model was performed on the basis of the calculation of the gas-phase binding enthalpies of base pairs obtained via potential of mean force calculations; the additive and polarizable models both performed satisfactorily with average differences of 0.2 and 0.9 kcal/mol, respectively, and rms differences of 1.3 and 1.7 kcal/mol, respectively. Overall, considering the number of significant improvements versus the additive CHARMM force field, the incorporation of explicit polarizability into the force field for nucleic acid bases represents an additional step toward accurate computational modeling of biological systems.

Dataset Information

CHARMM Drude Polarizable Force Field for Glycosidic Linkages Involving Pyranoses and Furanoses.

Publications

CHARMM Drude Polarizable Force Field for Glycosidic Linkages Involving Pyranoses and Furanoses.

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