Diffraction before destruction Chapman, Henry N.; Caleman, Carl; Timneanu, Nicusor
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
07/2014, Letnik:
369, Številka:
1647
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X-ray free-electron lasers have opened up the possibility of structure determination of protein crystals at room temperature, free of radiation damage. The femtosecond-duration pulses of these ...sources enable diffraction signals to be collected from samples at doses of 1000 MGy or higher. The sample is vaporized by the intense pulse, but not before the scattering that gives rise to the diffraction pattern takes place. Consequently, only a single flash diffraction pattern can be recorded from a crystal, giving rise to the method of serial crystallography where tens of thousands of patterns are collected from individual crystals that flow across the beam and the patterns are indexed and aggregated into a set of structure factors. The high-dose tolerance and the many-crystal averaging approach allow data to be collected from much smaller crystals than have been examined at synchrotron radiation facilities, even from radiation-sensitive samples. Here, we review the interaction of intense femtosecond X-ray pulses with materials and discuss the implications for structure determination. We identify various dose regimes and conclude that the strongest achievable signals for a given sample are attained at the highest possible dose rates, from highest possible pulse intensities.
The chemical composition of small organic molecules is often very similar to amino acid side chains or the bases in nucleic acids, and hence there is no a priori reason why a molecular mechanics ...force field could not describe both organic liquids and biomolecules with a single parameter set. Here, we devise a benchmark for force fields in order to test the ability of existing force fields to reproduce some key properties of organic liquids, namely, the density, enthalpy of vaporization, the surface tension, the heat capacity at constant volume and pressure, the isothermal compressibility, the volumetric expansion coefficient, and the static dielectric constant. Well over 1200 experimental measurements were used for comparison to the simulations of 146 organic liquids. Novel polynomial interpolations of the dielectric constant (32 molecules), heat capacity at constant pressure (three molecules), and the isothermal compressibility (53 molecules) as a function of the temperature have been made, based on experimental data, in order to be able to compare simulation results to them. To compute the heat capacities, we applied the two phase thermodynamics method (Lin et al. J. Chem. Phys. 2003, 119, 11792), which allows one to compute thermodynamic properties on the basis of the density of states as derived from the velocity autocorrelation function. The method is implemented in a new utility within the GROMACS molecular simulation package, named g_dos, and a detailed exposé of the underlying equations is presented. The purpose of this work is to establish the state of the art of two popular force fields, OPLS/AA (all-atom optimized potential for liquid simulation) and GAFF (generalized Amber force field), to find common bottlenecks, i.e., particularly difficult molecules, and to serve as a reference point for future force field development. To make for a fair playing field, all molecules were evaluated with the same parameter settings, such as thermostats and barostats, treatment of electrostatic interactions, and system size (1000 molecules). The densities and enthalpy of vaporization from an independent data set based on simulations using the CHARMM General Force Field (CGenFF) presented by Vanommeslaeghe et al. (J. Comput. Chem. 2010, 31, 671) are included for comparison. We find that, overall, the OPLS/AA force field performs somewhat better than GAFF, but there are significant issues with reproduction of the surface tension and dielectric constants for both force fields.
GROMACS molecule & liquid database van der Spoel, David; van Maaren, Paul J; Caleman, Carl
Bioinformatics (Oxford, England),
03/2012, Letnik:
28, Številka:
5
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MOTIVATION: The molecular dynamics simulation package GROMACS is a widely used tool used in a broad range of different applications within physics, chemistry and biology. It is freely available, user ...friendly and extremely efficient. The GROMACS software is force field agnostic, and compatible with many molecular dynamics force fields; coarse-grained, unified atom, all atom as well as polarizable models based on the charge on a spring concept. To validate simulations, it is necessary to compare results from the simulations to experimental data. To ease the process of setting up topologies and structures for simulations, as well as providing pre-calculated physical properties along with experimental values for the same we provide a web-based database, containing 145 organic molecules at present. RESULTS: Liquid properties of 145 organic molecules have been simulated using two different force fields, OPLS all atom and Generalized Amber Force Field. So far, eight properties have been calculated (the density, enthalpy of vaporization, surface tension, heat capacity at constant volume and pressure, isothermal compressibility, volumetric expansion coefficient and the static dielectric constant). The results, together with experimental values are available through the database, along with liquid structures and topologies for the 145 molecules, in the two force fields. AVAILABILITY: The database is freely available under http://virtualchemistry.org. CONTACT: spoel@xray.bmc.uu.se; carl.caleman@cfel.de
Water is a demanding partner. It strongly attracts ions, yet some halide anions--chloride, bromide, and iodide--are expelled to the air/water interface. This has important implications for chemistry ...in the atmosphere, including the ozone cycle. We present a quantitative analysis of the energetics of ion solvation based on molecular simulations of all stable alkali and halide ions in water droplets. The potentials of mean force for Clâ», Brâ», and Iâ» have shallow minima near the surface. We demonstrate that these minima derive from more favorable water-water interaction energy when the ions are partially desolvated. Alkali cations are on the inside because of the favorable ion-water energy, whereas Fâ» is driven inside by entropy. Models attempting to explain the surface preference based on one or more ion properties such as polarizability or size are shown to lead to qualitative and quantitative errors, prompting a paradigm shift in chemistry away from such simplifications.
Noroviruses are the major cause of viral gastroenteritis and re-emerge worldwide every year, with GII.4 currently being the most frequent human genotype. The norovirus capsid protein VP1 is essential ...for host immune response. The P domain mediates cell attachment via histo blood-group antigens (HBGAs) in a strain-dependent manner but how these glycan-interactions actually relate to cell entry remains unclear. Here, hydrogen/deuterium exchange mass spectrometry (HDX-MS) is used to investigate glycan-induced protein dynamics in P dimers of different strains, which exhibit high structural similarity but different prevalence in humans. While the almost identical strains GII.4 Saga and GII.4 MI001 share glycan-induced dynamics, the dynamics differ in the emerging GII.17 Kawasaki 308 and rare GII.10 Vietnam 026 strain. The structural aspects of glycan binding to fully deamidated GII.4 P dimers have been investigated before. However, considering the high specificity and half-life of N373D under physiological conditions, large fractions of partially deamidated virions with potentially altered dynamics in their P domains are likely to occur. Therefore, we also examined glycan binding to partially deamidated GII.4 Saga and GII.4 MI001 P dimers. Such mixed species exhibit increased exposure to solvent in the P dimer upon glycan binding as opposed to pure wildtype. Furthermore, deamidated P dimers display increased flexibility and a monomeric subpopulation. Our results indicate that glycan binding induces strain-dependent structural dynamics, which are further altered by N373 deamidation, and hence hint at a complex role of deamidation in modulating glycan-mediated cell attachment in GII.4 strains.
The bright ultrafast pulses of X-ray Free-Electron Lasers allow investigation into the structure of matter under extreme conditions. We have used single pulses to ionize and probe water as it ...undergoes a phase transition from liquid to plasma. We report changes in the structure of liquid water on a femtosecond time scale when irradiated by single 6.86 keV X-ray pulses of more than 10⁶ J/cm². These observations are supported by simulations based on molecular dynamics and plasma dynamics of a water system that is rapidly ionized and driven out of equilibrium. This exotic ionic and disordered state with the density of a liquid is suggested to be structurally different from a neutral thermally disordered state.
Single-particle imaging using X-ray free-electron lasers is an emerging technique that could provide high-resolution structures of macromolecules in the gas phase. One of the largest difficulties in ...realizing this goal is the unknown orientation of the individual sample molecules at the time of exposure. Preorientation of the molecules has been identified as a possible solution to this problem. Using molecular dynamics simulations, we identify a range of electric field strengths where proteins become oriented without losing their structure. For a number of experimentally relevant cases we show that structure determination is possible only when orientation information is included in the orientation-recovery process. We conclude that nondestructive field orientation of intact proteins is feasible and that it enables a range of new structural investigations with single-particle imaging.
Speckle contrast of interfering fluorescence X‐rays Trost, Fabian; Ayyer, Kartik; Oberthuer, Dominik ...
Journal of synchrotron radiation,
January 2023, 2023-Jan-01, 2023-01-01, 20230101, 2023, Letnik:
30, Številka:
1
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With the development of X‐ray free‐electron lasers (XFELs), producing pulses of femtosecond durations comparable with the coherence times of X‐ray fluorescence, it has become possible to observe ...intensity–intensity correlations due to the interference of emission from independent atoms. This has been used to compare durations of X‐ray pulses and to measure the size of a focusedX‐ray beam, for example. Here it is shown that it is also possible to observe the interference of fluorescence photons through the measurement of the speckle contrast of angle‐resolved fluorescence patterns. Speckle contrast is often used as a measure of the degree of coherence of the incident beam or the fluctuations of the illuminated sample as determined from X‐ray diffraction patterns formed by elastic scattering, rather than from fluorescence patterns as addressed here. Commonly used approaches to estimate speckle contrast were found to suffer when applied to XFEL‐generated fluorescence patterns due to low photon counts and a significant variation of the excitation pulse energy from shot to shot. A new method to reliably estimate speckle contrast under such conditions, using a weighting scheme, is introduced. The method is demonstrated by comparing the speckle contrast of fluorescence observed with pulses of 3 fs to 15 fs duration.
Methods are developed to quantify the degree of coherence of fluorescently emitted X‐rays from short‐pulse XFEL excitations. Applications to 3 fs and 15 fs excitations are shown.
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