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DNA is found in a dynamic equilibrium between standard Watson-Crick (WC) base pairs and non-standard Hoogsteen (HG) base pairs. Here the authors describe the influence of echinomycin and actinomycin D ligands binding on the HG-WC base pair dynamics in DNA.

We investigate theelectrostatics, energetics, and dynamics ofdendrimer–DNA interactions that mimic protein–DNA complexesas a means to design facilitated mechanisms by which dendrimers canslide and search DNA for targets. By using all-atom molecular dynamicssimulations, we calculated the free energy profiles of dendrimer-bindingaround the DNA via umbrella sampling. We also calculated electrostaticinteraction maps in comparison to proteins, as well as the dynamicalchanges induced by DNA–dendrimer interactions via NMR-measurableorder parameters. Our results show that for dendrimers to go aroundDNA, there is a free-energy barrier of 8.5 kcal/mol from the DNA majorgroove to DNA minor groove, with a minimum in the major groove. Thisbarrier height makes it unlikely for an all-amine dendrimer to slidealong DNA longitudinally, but following a helical path may be possiblealong the major groove. Comparison of the nonbonded interaction energyand the interaction free-energy profiles reveal a considerable entropiccost as the dendrimer binds to DNA. This is also supported by themobility patterns obtained from NMR-measurable order parameter values,which show a decreased mobility of the dendrimer N–H bond vectorsin the DNA-binding mode. [ABSTRACT FROM AUTHOR]

We combined molecular dynamics based free energy calculations with sum frequency generation (SFG) spectroscopy to study the orientational distribution of solvated peptides near hydrophobic surfaces. Using a simplified atomistic model of the polystyrene (PS) surface, molecular dynamics simulations have been applied to compute the orientational probability of an α-helical peptide, magainin 2, with respect to the PS/water interface. Free energy calculations revealed that the preferred (horizontal) peptide orientation was driven by the favorable interactions between the hydrophobic PS surface and the hydrophobic residues on the helix, and additional simulations examined the importance of small aggregate formation. Concentration-dependent measurements obtained via SFG vibrational spectroscopy suggest that, at very low peptide concentrations, magainin molecules tend to lie down at the PS/solution interface, which correlates well with the simulation results. When the concentration is increased, peptides exhibit behavior not captured by MD simulations using single helical peptides. A combination of simulations and experiments was shown to yield more reliable results with molecular-level insights into interaction between peptides and polymer surfaces. [ABSTRACT FROM AUTHOR]

Dynamic disorder in proteins, as demonstrated by variations in single-molecule electron transfer rates, is investigated by molecular dynamics simulations. The potential of mean force for the fluctuating donor−acceptor distance is calculated for the NAD(P)H:flavin oxidoreductase (Fre) complex with flavin adenine dinucleotide (FAD) and is found to be in agreement with that estimated from electron transfer experiments. The calculated autocorrelation function of the distance fluctuations has a simple exponential behavior at low temperatures and stretched exponential behavior at higher temperatures on femtosecond to nanosecond time scales. This indicates that the calculated dynamic disorder arises from a wide range of trapping times in potential wells on the protein energy landscape and suggests a corresponding origin for the stretched exponential behavior observed experimentally on longer time scales. [ABSTRACT FROM AUTHOR]