Systematic detection of hidden complexities in the unfolding mechanism of a cytosine-rich DNA strand

Smiatek, Jens; Janssen‐Müller, Daniel; Friedrich, Rudolf; Heuer, Andreas

doi:10.1016/j.physa.2013.09.030

Cited by 9 publications

(11 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the direct evaluation of free energy landscapes by free energy methods like metadynamics or umbrella sampling might also lead to wrong results due to inappropriate reaction coordinates and the presence of hysteresis effects. 72 Thus, the usage of restrained PNIPAM conformations as reference states avoids these drawbacks and provides a meaningful interpretation of the observed effects. 27,40 2.5 Implications of the Kirkwood-Buff theory and local/bulk partition coefficients The Kirkwood-Buff (KB) integral is given by…”

Section: Simulation Detailsmentioning

confidence: 99%

Concentration dependent effects of urea binding to poly(N-isopropylacrylamide) brushes: a combined experimental and numerical study

Micciulla

Michalowsky

Schroer

et al. 2016

Phys. Chem. Chem. Phys.

Self Cite

View full text Add to dashboard Cite

The binding effects of osmolytes on the conformational behavior of grafted polymers are studied in this work. In particular, we focus on the interactions between urea and poly(N-isopropylacrylamide) (PNIPAM) brushes by monitoring the ellipsometric brush thickness for varying urea concentrations over a broad temperature range. The interpretation of the obtained data is supported by atomistic molecular dynamics simulations, which provide detailed insights into the experimentally observed concentration-dependent effects on PNIPAM-urea interaction. In particular, in the low concentration regime (cu ≤ 0.5 mol L(-1)) a preferential exclusion of urea from PNIPAM chains is observed, while in the high concentration regime (2 ≤ cu ≤ 7 mol L(-1)) a preferential binding of the osmolyte to the polymer surface is found. In both regimes, the volume phase transition temperature (Ttr) decreases with increasing urea concentration. This phenomenon derives from two different effects depending on urea concentration: (i) for cu ≤ 0.5 mol L(-1), the decrease of Ttr is explained by a decrease of the chemical potential of bulk water in the surrounding aqueous phase; (ii) for cu ≥ 2 mol L(-1), the lower Ttr is explained by the favorable replacement of water molecules by urea, which can be regarded as a cross-linker between adjacent PNIPAM chains. Significant effects of the concentration-dependent urea binding on the brush conformation are noticed: at cu = 0.5 mol L(-1), although urea is loosely embedded between the hydrated polymer chains, it enhances the brush swelling by excluded volume effects. Beyond 0.5 mol L(-1), the stronger interaction between PNIPAM and urea reduces the chain hydration, which in combination with cross-linking of monomer units induces the shrinkage of the polymer brush.

show abstract

Section: Simulation Detailsmentioning

confidence: 99%

Concentration dependent effects of urea binding to poly(N-isopropylacrylamide) brushes: a combined experimental and numerical study

Micciulla

Michalowsky

Schroer

et al. 2016

Phys. Chem. Chem. Phys.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The importance of these and other higher-order DNA structures, besides further technological applications, relies on their pronounced relation between structure and function (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). Under slight changes of the environmental conditions, one can also recognize a strong tendency to unfold, which has some important consequences for biological functionality (54)(55)(56). As an often-studied example, a pronounced unfolding tendency in the presence of divalent cations was observed for single-stranded DNA structures (29,30).…”

Section: Introductionmentioning

confidence: 99%

Preferential Binding of Urea to Single-Stranded DNA Structures: A Molecular Dynamics Study

Oprzeska-Zingrebe

Smiatek

2018

Biophysical Journal

Self Cite

View full text Add to dashboard Cite

In nature, a wide range of biological processes such as transcription termination and intermolecular binding depend on the formation of specific DNA secondary and tertiary structures. These structures can be both stabilized or destabilized by different cosolutes coexisting with nucleic acids in the cellular environment. In our molecular dynamics simulation study, we investigate the binding of urea at different concentrations to short 7-nucleotide single-stranded DNA structures in aqueous solution. The local concentration of urea around a native DNA hairpin in comparison to an unfolded DNA conformation is analyzed by a preferential binding model in light of the Kirkwood-Buff theory. All our findings indicate a pronounced accumulation of urea around DNA that is driven by a combination of electrostatic and dispersion interactions and accomplished by a significant replacement of hydrating water molecules. The outcomes of our study can be regarded as a first step into a deeper mechanistic understanding toward cosolute-induced effects on nucleotide structures in general.

show abstract

“…The unfolded structure has been obtained by high temperature simulations at 500 K which gave us also the chance to find appropriate collective variables for the metadynamics simulations to clearly distinguish between the folded and the unfolded conformation. 49,50 Each production run of the restrained simulations had a length of 100 ns and was performed in an NpT ensemble at 298 K and 1 bar. More details on the simulation protocol can be found in the ESI.…”

mentioning

confidence: 99%

Peptides in the presence of aqueous ionic liquids: tunable co-solutes as denaturants or protectants?

Lesch

Heuer

Tatsis

et al. 2015

Phys. Chem. Chem. Phys.

Self Cite

View full text Add to dashboard Cite

We studied the stability of a small β-hairpin peptide under the influence of an aqueous 1-ethyl-3-methylimidazolium acetate ([EMIM](+)[ACE](-)) solution via all-atom molecular dynamics simulations in combination with metadynamics. Our free energy results indicate a denaturation of the peptide structure in the presence of the ionic liquid which is validated by a significant broadening of the end-to-end distance. The radial distribution functions between the ions and the peptide were used for the calculation of the preferential binding coefficients in terms of the Kirkwood-Buff theory. A significant structure dependent binding behavior of acetate to the peptide was found which can be interpreted as the main reason for the denaturation of the native conformation. The outcomes of our simulations allow us to propose a simple mechanism to explain the unfolding of the peptide with regard to the specific properties of ionic liquids. Our results are in good agreement with experimental findings and demonstrate the benefits of ionic liquids as tunable co-solutes with regard to their influence on protein structural properties.

show abstract

Systematic detection of hidden complexities in the unfolding mechanism of a cytosine-rich DNA strand

Cited by 9 publications

References 46 publications

Concentration dependent effects of urea binding to poly(N-isopropylacrylamide) brushes: a combined experimental and numerical study

Concentration dependent effects of urea binding to poly(N-isopropylacrylamide) brushes: a combined experimental and numerical study

Preferential Binding of Urea to Single-Stranded DNA Structures: A Molecular Dynamics Study

Peptides in the presence of aqueous ionic liquids: tunable co-solutes as denaturants or protectants?

Contact Info

Product

Resources

About