Most molecular dynamics (MD) simulations of DNA quadruplexes have been performed under minimal salt conditions using the Åqvist potential parameters for the cation with the TIP3P water model. Recently, this combination of parameters has been reported to be problematic for the stability of quadruplex DNA, especially caused by the ion interactions inside or near the quadruplex channel. Here, we verify how the choice of ion parameters and water model can affect the quadruplex structural stability and the interactions with the ions outside the channel. We have performed a series of MD simulations of the human full-parallel telomeric quadruplex by neutralizing its negative charge with K(+) ions. Three combinations of different cation potential parameters and water models have been used: (a) Åqvist ion parameters, TIP3P water model; (b) Joung and Cheatham ion parameters, TIP3P water model; and (c) Joung and Cheatham ion parameters, TIP4Pew water model. For the combinations (b) and (c), the effect of the ionic strength has been evaluated by adding increasing amounts of KCl salt (50, 100, and 200 mM). Two independent simulations using the Åqvist parameters with the TIP3P model show that this combination is clearly less suited for the studied quadruplex with K(+) as counterions. In both simulations, one ion escapes from the channel, followed by significant deformation of the structure, leading to deviating conformation compared to that in the reference crystallographic data. For the other combinations of ion and water potentials, no tendency is observed for the channel ions to escape from the quadruplex channel. In addition, the internal mobility of the three loops, torsion angles, and counterion affinity have been investigated at varied salt concentrations. In summary, the selection of ion and water models is crucial as it can affect both the structure and dynamics as well as the interactions of the quadruplex with its counterions. The results obtained with the TIP4Pew model are found to be closest to the experimental data at all of the studied ion concentrations.

Surface-enhanced Raman spectroscopy, resonance Raman spectroscopy and molecular modeling were employed to study the interaction of hypericin (Hyp) with human (HSA), rat (RSA) and bovine (BSA) serum albumins. The identification of the binding site of Hyp in serum albumins as well as the structural model for Hyp/HSA complex are presented. The interactions mainly reflect: (1) a change of the strength of H bonding at the N1-H site of Trp; (2) a change of the Trp side-chain conformation; (3) a change of the hydrophobicity of the Trp environment; and (4) a formation of an H-bond between the carbonyl group of Hyp and a proton donor in HSA and RSA which leads to a protonated-like carbonyl in Hyp. Our results indicate that Hyp is rigidly bound in IIA subdomain of HSA close to Trp214 (distance 5.12 A between the centers of masses). In the model presented the carbonyl group of Hyp is hydrogen bonded to Asn458. Two other candidates for hydrogen bonds have been identified between the bay-region hydroxyl group of Hyp and the carbonyl group of the Trp214 peptidic link and between the peri-region hydroxyl group of Hyp and the Asn458 carbonyl group. It is shown that the structures of the Hyp/HSA and Hyp/RSA complexes are similar to, and in some aspects different from, those found for the Hyp/BSA complex. The role of aminoacid sequence in the IIA subdomains of HSA, RSA and BSA is discussed to explain the observed differences.

We demonstrate X-ray phase contrast microscopy performed at the European X-ray Free-Electron Laser sampled at 1.128 MHz rate. We have applied this method to image stochastic processes induced by an optical laser incident on water-filled capillaries with micrometer scale spatial resolution. The generated high speed water jet, cavitation formation and annihilation in water and glass, as well as glass explosions are observed. The comparison between XFEL and previous synchrotron MHz microscopy shows the superior contrast and spatial resolution at the XFEL over the synchrotron. This work opens up new possibilities for the characterization of dynamic stochastic systems on nanosecond to microsecond time scales at megahertz rate with object velocities up to few kilometers per second using X-ray Free-Electron Laser sources.Hard X-ray beams are well suited for microscopic 2D and 3D imaging of samples not transparent to visible light due to their high penetration power. Over the last two decades the field of X-ray imaging has developed considerably, mainly due to the availability of modern, third-generation synchrotrons producing X-rays of high brilliance [1]. These sources have provided access to the structural determination of specimens down to nano meter scale resolutions. Exploiting the (partial) spatial coherence of synchrotron X-ray probes, several phase sensitive techniques have been developed providing access to the electron density of specimens either via X-ray optical analyzers [2][3][4] or sophisticated algorithms [5,6]. While much attention has been paid to improve the spatial resolution of X-ray imaging to its limits, fewer resources have been used to explore the boundaries of the temporal domain. With the progress in the development of detectors over the last decade [7], fast radiography and tomography with kilohertz frame rates are available allowing, for example,~100 tomograms per second [8,9]. Only relatively recently has the stroboscopic nature arXiv:1906.07263v1 [physics.ins-det]

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The photochemistry of Urocanic acid, a chromophore present in human skin and linked to photoimmunosuppression and skin cancer, is investigated theoretically by means of time-dependent density functional theory. Extensive calculations are carried out for different ionic, rotameric, and protomeric forms of both the trans and cis form. Inclusion of solvation effects, here accounted for by means of a continuum solvent model, are found to be crucial for the correct description of the biologically relevant zwitterionic forms of the molecule. For the trans zwitterionic form, it is found that the planar form usually assumed in the literature is not stable, and that a realistic charge separation cannot be achieved in the gas phase. Calculated vertical excitation energies are in excellent agreement with available experimental data, with a weakly absorbing n --> pi transition around 4.0 eV, and strongly absorbing pi --> pi transitions at 4.5-4.9 eV. The debated intramolecular hydrogen bond is predicted to have a modest impact on the vertical spectra in solution, but improves agreement with experiment when included. In general, we also predict that different rotameric forms have very similar absorption spectra. In addition, we find a candidate absorbing state to link trans-urocanic acid to singlet oxygen production and subsequent photoaging of the skin.