Structure of hen egg-white lysozyme solvated in TFE/water: a molecular dynamics simulation study based on NMR data

Eichenberger, Andreas P.; Gunsteren, Wilfred F. van; Smith, Lorna J.

doi:10.1007/s10858-013-9717-y

Cited by 11 publications

(8 citation statements)

References 42 publications

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“…The accuracy with which the molecular model mimics these interactions has an impact on the accumulation behavior of TMAO around proteins and thus on the thermodynamic equilibrium between different protein conformations observed in the simulation. These effects can be quantified using the potential distribution theorem or the Kirkwood-Buff theory. − If an atom-based cosolute model has been validated against independent data and turns out to reproduce in addition the macroscopic effect of interest, then it can tentatively be used to interpret this effect in physical terms. − Our work thus represents a valuable supplement to the recently performed TMAO force-field comparison reported by Rodrı́guez-Ropero et al, which was mainly focused on the impact of TMAO on the folding equilibrium of a hydrophobic model polymer, but also investigated quantities of aqueous solutions such as surface tension, osmotic coefficient, as well as the transfer free energy of neopentane from pure water to 1 molar TMAO solution.…”

Section: Introductionmentioning

confidence: 81%

Validation of Trimethylamine-N-oxide (TMAO) Force Fields Based on Thermophysical Properties of Aqueous TMAO Solutions

et al. 2017

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Five molecular models for trimethylamine N-oxide (TMAO) to be used in conjunction with compatible models for liquid water are evaluated by comparison of molecular dynamics (MD) simulation results to experimental data as functions of TMAO molality. The experimental data comprise thermodynamic properties (density, apparent molar volume, and partial molar volume at infinite dilution), transport properties (self-diffusion and shear viscosity), structural properties (radial distribution functions and degree of hydrogen bonding), and dielectric properties (dielectric spectra and static permittivity). The thermodynamic and transport properties turned out to be useful in TMAO model discrimination while the influence of the water model and the TMAO-water interaction are effectively probed through the calculation of dielectric spectra.

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Section: Introductionmentioning

confidence: 81%

Validation of Trimethylamine-N-oxide (TMAO) Force Fields Based on Thermophysical Properties of Aqueous TMAO Solutions

et al. 2017

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“…Unlike other computational studies of TFE - peptide/protein interactions, ,− our study attempted to quantify the effect of TFE on helical propensity, and we analyzed this effect in the framework of the Lifson–Roig model and preferential interactions. Although the form of the L–R model used in our study is very approximative, our numerical fits can provide at least qualitative insight into the thermodynamics of the helix–coil transition.…”

Section: Discussionmentioning

confidence: 99%

Effect of TFE on the Helical Content of AK17 and HAL-1 Peptides: Theoretical Insights into the Mechanism of Helix Stabilization

2016

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Fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) are among the most frequently used cosolvents in experiment studies of peptides. They have significant effects on secondary structure and a particularly strong promotion of α-helix is induced by TFE. In this study we validated recently proposed force field parameters for TFE in molecular dynamics simulations with two model peptides-alanine-rich AK-17 and antimicrobial peptide halictine-1 (HAL-1). In the case of HAL-1, we characterized the effect of TFE on this peptide experimentally by ECD spectroscopy. Our TFE model in question reproduced the helix-promoting effect of TFE and provided insight into the mechanisms of TFE action on peptides. Our simulations confirmed the preferential interaction of TFE molecules with α-helices, although the TFE molecules accumulate in the vicinity of the peptides in various conformations. Moreover, we observed a significant effect of TFE on the thermodynamics of the helix-coil transition and a change in local conformational preferences in the unfolded (coil) state induced by TFE. In addition, our simulation-based analysis suggests that different mechanisms participate in helix stabilization in both model peptides in water and TFE solution. Our results thus support the picture of complex TFE action on peptides that is further diversified by the identity and intrinsic properties of the peptide.

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“…It has been shown that the local structure change relates with the local dynamics or entropy change. [40][41][42] In order to understand the structure and dynamics of hBD-3 and HD5 in both oxidizing and reducing conditions, quasi-harmonic entropy of cysteine residue pairs for both kinds of defensins was calculated using the Wordom program with results shown in Table V. The entropy for the wildtype was calculated based on the microsecond simulation trajectories for both kinds of defensins.…”

Section: Entropy Calculationmentioning

confidence: 99%

Different dynamics and pathway of disulfide bonds reduction of two human defensins, a molecular dynamics simulation study

Zhang

2017

Proteins

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Human defensins are a class of antimicrobial peptides that are crucial components of the innate immune system. Both human α defensin type 5 (HD5) and human β defensin type 3 (hBD-3) have 6 cysteine residues which form 3 pairs of disulfide bonds in oxidizing condition. Disulfide bond linking is important to the protein structure stabilization, and the disulfide bond linking and breaking order have been shown to influence protein function. In this project, microsecond long molecular dynamics simulations were performed to study the structure and dynamics of HD5 and hBD-3 wildtype and analogs which have all 3 disulfide bonds released in reducing condition. The structure of hBD-3 was found to be more dynamic and flexible than HD5, based on RMSD, RMSF, and radius of gyration calculations. The disulfide bridge breaking order of HD5 and hBD-3 in reducing condition was predicted by two kinds of methods, which gave consistent results. It was found that the disulfide bonds breaking pathways for HD5 and hBD-3 are very different. The breaking of disulfide bonds can influence the dimer interface by making the dimer structure less stable for both kinds of defensin. In order to understand the difference in dynamics and disulfide bond breaking pathway, hydrophilic and hydrophobic accessible surface areas (ASA), buried surface area between cysteine pairs, entropy of cysteine pairs, and internal energy were calculated. Comparing to the wildtype, hBD-3 analog is more hydrophobic, while HD5 is more hydrophilic. For hBD-3, the disulfide breaking is mainly entropy driven, while other factors such as the solvation effects may take the major role in controlling HD5 disulfide breaking pathway. Proteins 2017; 85:665-681. © 2016 Wiley Periodicals, Inc.

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Structure of hen egg-white lysozyme solvated in TFE/water: a molecular dynamics simulation study based on NMR data

Cited by 11 publications

References 42 publications

Validation of Trimethylamine-N-oxide (TMAO) Force Fields Based on Thermophysical Properties of Aqueous TMAO Solutions

Validation of Trimethylamine-N-oxide (TMAO) Force Fields Based on Thermophysical Properties of Aqueous TMAO Solutions

Effect of TFE on the Helical Content of AK17 and HAL-1 Peptides: Theoretical Insights into the Mechanism of Helix Stabilization

Different dynamics and pathway of disulfide bonds reduction of two human defensins, a molecular dynamics simulation study

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