Dataset Information

Proper balance of solvent-solute and solute-solute interactions in the treatment of the diffusion of glucose using the Drude polarizable force field.

ABSTRACT: Motivated by underestimation of the diffusion constant of glucose in aqueous solution at high glucose concentrations we performed additional optimization of the Drude polarizable hexopyranose monosaccharide force field. This indicated aggregation of the glucose at higher concentrations, which is a concern for studies of complex glycan systems such as the HIV Envelope where high effective concentrations of sugars are present. High-level quantum mechanical calculations were undertaken on water monohydrate-glucose interactions, on water cluster-glucose interactions and on glucose-glucose dimers in stacked (parallel) and perpendicular orientations. Optimization of the nonbond and dihedral parameters targeting these data yielded a revised model that showed improved agreement with experimental aqueous diffusion data. However, limitations in the diffusion constants were still present. These were due to the SWM4-NDP inherently overestimating the diffusion constant of water, a problem that was validated by calculation of the aqueous diffusion constants using the SWM6-NDP water model. In addition, results show the water diffusion constant to be significantly overestimated at high glucose concentrations though the glucose diffusion is in satisfactory agreement with experiment. These results indicate the subtle balance of water-sugar, water-water and sugar-sugar interactions that needs to be properly modeled to account for the full range of aqueous behavior of sugars in aqueous solution.

SUBMITTER: Yang M

PROVIDER: S-EPMC5809005 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

Proper balance of solvent-solute and solute-solute interactions in the treatment of the diffusion of glucose using the Drude polarizable force field.

Yang Mingjun M Aytenfisu Asaminew H AH MacKerell Alexander D AD

Carbohydrate research 20180131

Motivated by underestimation of the diffusion constant of glucose in aqueous solution at high glucose concentrations we performed additional optimization of the Drude polarizable hexopyranose monosaccharide force field. This indicated aggregation of the glucose at higher concentrations, which is a concern for studies of complex glycan systems such as the HIV Envelope where high effective concentrations of sugars are present. High-level quantum mechanical calculations were undertaken on water mon ...[more]

PMID: 29422120

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Project description:The CHARMM Drude-2013 polarizable force field (FF) was developed to include the explicit treatment of induced electronic polarizability, resulting in a more accurate description of the electrostatic interactions in molecular dynamics (MD) simulations. While the Drude-2013 protein FF has shown success in improving the folding properties of α-helical peptides and to reproduce experimental observables in simulations up to 1 μs, some limitations were noted regarding the stability of β-sheet structures in simulations longer than 100 ns as well as larger deviations from crystal structures in simulations of a number of proteins compared to the additive CHARMM36 protein FF. The origin of the instability has been identified and appears to be primarily due to overestimated atomic polarizabilities and induced dipole-dipole interactions on the Cβ, Cγ, and Cδ side chain atoms. To resolve this and other issues, a number of aspects of the model were revisited, resulting in Drude-2019 protein FF. Backbone parameters were optimized targeting the conformational properties of the (Ala)5 peptide in solution along with gas phase properties of the alanine dipeptide. Dipeptides that contain N-acetylated and N'-methylamidated termini, excluding Gly, Pro, and Ala, were used as models to optimize the atomic polarizabilities and Thole screening factors on selected Cβ, Cγ, and Cδ carbons by targeting quantum mechanical (QM) dipole moments and molecular polarizabilities. In addition, to obtain better conformational properties, side chain χ1 and χ2 dihedral parameters were optimized targeting QM data for the respective side chain dipeptide conformations as well as Protein Data Bank survey data based on the χ1, χ2 sampling from Hamiltonian replica-exchange MD simulations of (Ala)4-X-(Ala)4 in solution, where X is the amino acid of interest. Further improvements include optimizing nonbonded interactions between charged residues to reproduce QM interaction energies of the charged-protein model compounds and experimental osmotic pressures. Validation of the optimized Drude protein FF includes MD simulations of a collection of peptides and proteins including β-sheet structures, as well as transmembrane ion channels. Results showed that the updated Drude-2019 protein FF yields smaller overall root-mean-square differences of proteins as compared to the additive CHARMM36m and Drude-2013 FFs as well as similar or improved agreement with experimental NMR properties, allowing for long time scale simulation studies of proteins and more complex biomolecular systems in conjunction with the remainder of the Drude polarizable FF.

Dataset Information

Proper balance of solvent-solute and solute-solute interactions in the treatment of the diffusion of glucose using the Drude polarizable force field.

Publications

Proper balance of solvent-solute and solute-solute interactions in the treatment of the diffusion of glucose using the Drude polarizable force field.

Similar Datasets

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