Single molecule imaging with longer x-ray laser pulses

During the last five years, serial femtosecond crystallography using x-ray laser pulses has developed into a powerful technique for determining the atomic structures of protein molecules from micrometer and sub-micrometer sized crystals. One of the key reasons for this success is the "self-gating" pulse effect, whereby the x-ray laser pulses do not need to outrun all radiation damage processes. Instead, x-ray induced damage terminates the Bragg diffraction prior to the pulse completing its passage through the sample, as if the Bragg diffraction was generated by a shorter pulse of equal intensity. As a result, serial femtosecond crystallography does not need to be performed with pulses as short as 5--10 fs, as once thought, but can succeed for pulses 50--100 fs in duration. We show here that a similar gating effect applies to single molecule diffraction with respect to spatially uncorrelated damage processes like ionization and ion diffusion. The effect is clearly seen in calculations of the diffraction contrast, by calculating the diffraction of average structure separately to the diffraction from statistical fluctuations of the structure due to damage ("damage noise"). Our results suggest that sub-nanometer single molecule imaging with 30--50 fs pulses, like those produced at currently operating facilities, should not yet be ruled out. The theory we present opens up new experimental avenues to measure the impact of damage on single particle diffraction, which is needed to test damage models and to identify optimal imaging conditions.Comment: 23 pages; 5 figure

Proton dynamics in molecular solvent clusters as an indicator for hydrogen bond network strength in confined geometries

Hydrogen bonding leads to the formation of strong, extended intermolecular networks in molecular liquids such as water. However, it is less well-known how robust the network is to environments in which surface formation or confinement effects become prominent, such as in clusters or droplets. Such systems provide a useful way to probe the robustness of the network, since the degree of confinement can be tuned by altering the cluster size, changing both the surface-to-volume ratio and the radius of curvature. To explore the formation of hydrogen bond networks in confined geometries, here we present O 1s Auger spectra of small and large clusters of water, methanol, and dimethyl ether, as well as their deuterated equivalents. The Auger spectra of the clusters and the corresponding macroscopic liquids are compared and evaluated for an isotope effect, which is due to proton dynamics within the lifetime of the core hole (proton-transfer-mediated charge-separation, PTM-CS), and can be linked to the formation of a hydrogen bond network in the system. An isotope effect is observed in water and methanol but not for dimethyl ether, which cannot donate a hydrogen bond at its oxygen site. The isotope effect, and therefore the strength of the hydrogen bond network, is more pronounced in water than in methanol. Its value depends on the average size of the cluster, indicating that confinement effects change proton dynamics in the core ionised excited state

Procesos de organización política de las mujeres indígenas en el movimiento amplio de mujeres en Argentina. Consideraciones sobre el feminismo desde la perspectiva indígena

We present a study of the characteristics of secondary electron cascades in two photocathode materials, KI and CsI. To do so, we have employed a model that enables us to explicitly follow the electron trajectories once the dielectric properties have been derived semiempirically from the energy loss function. Furthermore, we introduce a modification to the model by which the energy loss function is calculated in a first-principle manner using the GW approximation for the self-energy of the electrons. We find good agreement between the two approaches. Our results show comparable saturation times and secondary electron yields for the cascades in the two materials, and a narrower electron energy distribution (51%) for KI compared to that for CsI

A Validation Study of the General Amber Force Field Applied to Energetic Molecular Crystals

Molecula dynamics is a well-established tool to computationally study molecules. However, to reach predictive capability at the level required for applied research and design, extensive validation of the available force fields is pertinent. Here we present a study of density, isothermal compressibility and coefficients of thermal expansion of four energetic materials (FOX-7, RDX, CL-20 and HMX) based on molecular dynamics simulations with the General Amber Force Field (GAFF), and compare the results to experimental measurements from the literature. Furthermore, we quantify the accuracy of the calculated properties through hydrocode simulation of a typical impact scenario. We find that molecular dynamics simulations with generic and computationally efficient force fields may be used to understand and estimate important physical properties of nitramine-like energetic materials

Secondary Electron Cascade Dynamics in KI and CsI

We present a study of the characteristics of secondary electron cascades in two photocathode materials, KI and CsI. To do so, we have employed a model that enables us to explicitly follow the electron trajectories once the dielectric properties have been derived semiempirically from the energy loss function. Furthermore, we introduce a modification to the model by which the energy loss function is calculated in a first-principle manner using the GW approximation for the self-energy of the electrons. We find good agreement between the two approaches. Our results show comparable saturation times and secondary electron yields for the cascades in the two materials, and a narrower electron energy distribution (51%) for KI compared to that for CsI

Charge State Dependence of Amino Acid Propensity at Water Surface : Mechanisms Elucidated by Molecular Dynamics Simulations

Atmospheric aerosols contain a variety of compounds, among them free amino acids and salt ions. The pH of the aerosol droplets depends on their origin and environment. Consequently, compounds like free amino acids found in the droplets will be at different charge states, since these states to a great extent depend on the surrounding pH condition. In droplets of marine origin, amino acids are believed to drive salt ions to the water surface and a pH-dependent amino acid surface propensity will, therefore, indirectly affect many processes in atmospheric chemistry and physics such as for instance cloud condensation. To understand the surface propensity of glycine, valine, and phenylalanine at acidic, neutral, and basic pH, we used molecular dynamics (MD) simulations to investigate them at three different charge states in water. Their respective surface propensities were obtained by the means of a potential of mean force (PMF) in an umbrella sampling approach. Glycine was found to have no preference for the surface, while both valine and phenylalanine showed high propensities. Among the charge states of the surface-enriched ones, the cation, representing the amino acids at low pH, was found to have the highest affinity. Free energy decomposition revealed that the driving forces depend strongly on the nature of the amino acid and its charge state. In phenylalanine, the main factor was found to be a substantial entropy gain, likely related to the side chain, whereas in valine, hydrogen bonding to the functional groups leads to favorable energies and, in turn, affects the surface propensity. A significant gain in water-water enthalpy was seen for both valine and phenylalanine

Distinguishing between Similar Miniproteins with Single-Molecule Nanopore Sensing : A Computational Study

A nanopore is a tool in single-molecule sensing biotechnology that offers label-free identification with high throughput. Nanopores have been successfully applied to sequence DNA and show potential in the study of proteins. Nevertheless, the task remains challenging due to the large variability in size, charges, and folds of proteins. Miniproteins have a small number of residues, limited secondary structure, and stable tertiary structure, which can offer a systematic way to reduce complexity. In this computational work, we theoretically evaluated sensing two miniproteins found in the human body using a silicon nitride nanopore. We employed molecular dynamics methods to compute occupied-pore ionic current magnitudes and electronic structure calculations to obtain interaction strengths between pore wall and miniprotein. From the interaction strength, we derived dwell times using a mix of combinatorics and numerical solutions. This latter approach circumvents typical computational demands needed to simulate translocation events using molecular dynamics. We focused on two miniproteins potentially difficult to distinguish owing to their isotropic geometry, similar number of residues, and overall comparable structure. We found that the occupied-pore current magnitudes not to vary significantly, but their dwell times differ by 1 order of magnitude. Together, these results suggest a successful identification protocol for similar miniproteins

Is Radiation Damage the Limiting Factor in Single Particle Imaging with X-ray Free-Electron Lasers?

The prospect of single particle imaging with atomic resolution is one of the scientific drivers for the development of X-ray free-electron lasers. The assumption since the beginning has been that damage to the sample caused by intense X-ray pulses is one of the limiting factors of coherent diffractive imaging of single particles and that X-ray pulses need to be as short as possible. Based on molecular dynamics simulations of proteins in X-ray fields of various durations (5 fs, 25 fs and 50 fs), we show that the noise in the diffracted signal caused by radiation damage is less than what can be expected from other sources, such as sample inhomogeneity and X-ray shot-to-shot variations. These findings show a different aspect of the feasibility of single particle imaging using free-electron lasers, where employing X-ray pulses of longer durations could still provide a useful diffraction signal above the noise due to the Coulomb explosion