Force-field dependence of the conformational properties of α,ω-dimethoxypolyethylene glycol

Winger, Moritz; Vries, Alex H. de; Gunsteren, Wilfred F. van

doi:10.1080/00268970902794826

Cited by 29 publications

(39 citation statements)

References 35 publications

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“…[25] The parameters for the sulfate ions, which were included in the abovementioned force field, had previously been used in investigations into conformational properties of organic molecules. [26,27] As reported previously, [11] the sulfate model in the GROMOS force field (Table 1) did not exhibit excessive clustering under ambient conditions, as reported for other force fields by Wernersson and Jungwirth, [28] and showed reasonable temperature-solubility relationships for Na 2 SO 4 . [11] The present simulations were conducted in the NVT ensemble with periodic boundary conditions between 25 and 320 8C( plus up to 420 8Ci nc ase of binary solutions of K 2 SO 4 ).…”

Section: Computationalmethodssupporting

confidence: 70%

“…Both alkali cation (Na, K) parameters were optimized according to the calculated solvation free energy . The parameters for the sulfate ions, which were included in the abovementioned force field, had previously been used in investigations into conformational properties of organic molecules . As reported previously, the sulfate model in the GROMOS force field (Table ) did not exhibit excessive clustering under ambient conditions, as reported for other force fields by Wernersson and Jungwirth, and showed reasonable temperature–solubility relationships for Na 2 SO 4 .…”

Section: Methodsmentioning

confidence: 73%

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Speciation and Structural Properties of Hydrothermal Solutions of Sodium and Potassium Sulfate Studied by Molecular Dynamics Simulations

2016

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Aqueous solutions of salts at elevated pressures and temperatures play a key role in geochemical processes and in applications of supercritical water in waste and biomass treatment, for which salt management is crucial for performance. A major question in predicting salt behavior in such processes is how different salts affect the phase equilibria. Herein, molecular dynamics (MD) simulations are used to investigate molecular-scale structures of solutions of sodium and/or potassium sulfate, which show contrasting macroscopic behavior. Solutions of Na-SO4 exhibit a tendency towards forming large ionic clusters with increasing temperature, whereas solutions of K-SO4 show significantly less clustering under equivalent conditions. In mixed systems (Nax K2-x SO4 ), cluster formation is dramatically reduced with decreasing Na/(K+Na) ratio; this indicates a structure-breaking role of K. MD results allow these phenomena to be related to the characteristics of electrostatic interactions between K(+) and SO4 (2-) , compared with the analogous Na(+) -SO4 (2-) interactions. The results suggest a mechanism underlying the experimentally observed increasing solubility in ternary mixtures of solutions of Na-K-SO4 . Specifically, the propensity of sodium to associate with sulfate, versus that of potassium to break up the sodium-sulfate clusters, may affect the contrasting behavior of these salts. Thus, mutual salting-in in ternary hydrothermal solutions of Na-K-SO4 reflects the opposing, but complementary, natures of Na-SO4 versus K-SO4 interactions. The results also provide clues towards the reported liquid immiscibility in this ternary system.

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Section: Computationalmethodssupporting

confidence: 70%

Section: Methodsmentioning

confidence: 73%

Speciation and Structural Properties of Hydrothermal Solutions of Sodium and Potassium Sulfate Studied by Molecular Dynamics Simulations

2016

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“…PEG parameterization was performed with quantum computation within Gaussian 09W [23], resultant parameters were integrated to the 53a6 force field to form a new force field, named 53a6_PEG. Its suitability for PEG simulation was validated by comparing its performance in PEG simulation to that of force field 53a6_OE developed in [24]. Figures S1 and S2 show that 53a6_PEG results in more extended PEG chains than 53a6_OE.…”

Section: Methodsmentioning

confidence: 99%

Molecular Insight into the Steric Shielding Effect of PEG on the Conjugated Staphylokinase: Biochemical Characterization and Molecular Dynamics Simulation

2013

PLoS ONE

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PEGylation is a successful approach to improve potency of a therapeutic protein. The improved therapeutic potency is mainly due to the steric shielding effect of PEG. However, the underlying mechanism of this effect on the protein is not well understood, especially on the protein interaction with its high molecular weight substrate or receptor. Here, experimental study and molecular dynamics simulation were used to provide molecular insight into the interaction between the PEGylated protein and its receptor. Staphylokinase (Sak), a therapeutic protein for coronary thrombolysis, was used as a model protein. Four PEGylated Saks were prepared by site-specific conjugation of 5 kDa/20 kDa PEG to N-terminus and C-terminus of Sak, respectively. Experimental study suggests that the native conformation of Sak is essentially not altered by PEGylation. In contrast, the bioactivity, the hydrodynamic volume and the molecular symmetric shape of the PEGylated Sak are altered and dependent on the PEG chain length and the PEGylation site. Molecular modeling of the PEGylated Saks suggests that the PEG chain remains highly flexible and can form a distinctive hydrated layer, thereby resulting in the steric shielding effect of PEG. Docking analyses indicate that the binding affinity of Sak to its receptor is dependent on the PEG chain length and the PEGylation site. Computational simulation results explain experimental data well. Our present study clarifies molecular details of PEG chain on protein surface and may be essential to the rational design, fabrication and clinical application of PEGylated proteins.

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“…Condensed-phase force fields such as CHARMM [5][6][7][8][9][10][11][12][13][14][15] , AMBER [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] , OPLS 32-44 , TraPPE [45][46][47][48][49][50][51][52] and GROMOS [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68] mainly aim at the description of solids, liquids and solutions, including solvated biomolecules as a particularly relevant special case. ...…”

Section: Introductionmentioning

confidence: 99%

A GROMOS-Compatible Force Field for Small Organic Molecules in the Condensed Phase: The 2016H66 Parameter Set

Horta

Merz

Fuchs

et al. 2016

J. Chem. Theory Comput.

139

287

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This article reports on the calibration and validation of a new GROMOS-compatible parameter set 2016H66 for small organic molecules in the condensed phase. The calibration is based on 62 organic molecules spanning the chemical functions alcohol, ether, aldehyde, ketone, carboxylic acid, ester, amine, amide, thiol, sulfide, and disulfide, as well as aromatic compounds and nucleic-acid bases. For 57 organic compounds, the calibration targets are the experimental pure-liquid density ρliq and the vaporization enthalpy ΔHvap, as well as the hydration free energy ΔGwat and the solvation free energy ΔGche in cyclohexane, at atmospheric pressure and at (or close to) room temperature. The final root-mean-square deviations (RMSD) for these four quantities over the set of compounds are 32.4 kg m(-3), 3.5 kJ mol(-1), 4.1 kJ mol(-1), and 2.1 kJ mol(-1), respectively, and the corresponding average deviations (AVED) are 1.0 kg m(-3), 0.2 kJ mol(-1), 2.6 kJ mol(-1), and 1.0 kJ mol(-1), respectively. For the five nucleic-acid bases, the parametrization is performed by transferring the final 2016H66 parameters from analogous organic compounds followed by a slight readjustment of the charges to reproduce the experimental water-to-chloroform transfer free energies ΔGtrn. The final RMSD for this quantity over the five bases is 1.7 kJ mol(-1), and the corresponding AVED is 0.8 kJ mol(-1). As an initial validation of the 2016H66 set, seven additional thermodynamic, transport, and dielectric properties are calculated for the 57 organic compounds in the liquid phase. The agreement with experiment in terms of these additional properties is found to be reasonable, with significant deviations typically affecting either a specific chemical function or a specific molecule. This suggests that in most cases, a classical force-field description along with a careful parametrization against ρliq, ΔHvap, ΔGwat, and ΔGche results in a model that appropriately describes the liquid in terms of a wide spectrum of its physical properties.

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Force-field dependence of the conformational properties of α,ω-dimethoxypolyethylene glycol

Cited by 29 publications

References 35 publications

Speciation and Structural Properties of Hydrothermal Solutions of Sodium and Potassium Sulfate Studied by Molecular Dynamics Simulations

Speciation and Structural Properties of Hydrothermal Solutions of Sodium and Potassium Sulfate Studied by Molecular Dynamics Simulations

Molecular Insight into the Steric Shielding Effect of PEG on the Conjugated Staphylokinase: Biochemical Characterization and Molecular Dynamics Simulation

A GROMOS-Compatible Force Field for Small Organic Molecules in the Condensed Phase: The 2016H66 Parameter Set

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