molecular properties – Lightsources.org

Calculating the “fingerprints” of molecules with artificial intelligence

2022/06/132022/06/28

With conventional methods, it is extremely time-consuming to calculate the spectral fingerprint of larger molecules. But this is a prerequisite for correctly interpreting experimentally obtained data. Now, a team at HZB has achieved very good results in significantly less time using self-learning graphical neural networks.

“Macromolecules but also quantum dots, which often consist of thousands of atoms, can hardly be calculated in advance using conventional methods such as DFT,” says PD Dr. Annika Bande at HZB. With her team she has now investigated how the computing time can be shortened by using methods from artificial intelligence.

The idea: a computer programme from the group of “graphical neural networks” or GNN receives small molecules as input with the task of determining their spectral responses. In the next step, the GNN programme compares the calculated spectra with the known target spectra (DFT or experimental) and corrects the calculation path accordingly. Round after round, the result becomes better. The GNN programme thus learns on its own how to calculate spectra reliably with the help of known spectra.

Direct observation of the ad- and desorption of guest atoms into a mesoporous host

2021/04/212021/04/22

Battery electrodes, storage devices for gases, and some catalyst materials have tiny functional pores that can accommodate atoms, ions, and molecules. How these guest atoms are absorbed into or released from the pores is crucial to understanding the porous materials’ functionality. However, usually these processes can only be observed indirectly. A team from the Helmholtz Zentrum Berlin (HZB) has employed two experimental approaches using the ASAXS instrument at the PTB X-ray beamline of the HZB BESSY II synchrotron to directly observe the adsorption process of atoms in a mesoporous model system. The work lays the foundations for new insights into these kinds of energy materials.

Most battery materials, novel catalysts, and storage materials for hydrogen have one thing in common: they have a structure comprised of tiny pores in the nanometer range. These pores provide space which can be occupied by guest atoms, ions, and molecules. As a consequence, the properties of the guest and the host can change dramatically. Understanding the processes inside the pores is crucial to develop innovative energy technologies.

Read more on the HZB website

Image: From the measurement data, the team was able to determine that the xenon atoms first accumulate on the inner walls of the pores (state 1), before they fill them up (state 2). The X-ray beam penetrates the sample from below.

Credit: © M. Künsting/HZB

How deadly parasites ‘glide’ into human cells

2020/10/262020/10/29

X-ray analysis reveals structure of molecular machinery of malaria and toxoplasmosis pathogens

An investigation at DESY’s X-ray source PETRA III provides new insights into the molecular machinery by which certain parasites travel through the human organism. The study, led by Christian Löw from the Hamburg branch of the European Molecular Biology Laboratory EMBL, analyzed the so-called gliding movement of the malaria and toxoplasmosis parasites. The results, which the interdisciplinary team presents in the journal Communications Biology, can aid the search for new drugs against the pathogens.

In biological terms, gliding refers to the type of movement during which a cell moves along a surface without changing its shape. This form of movement is unique to parasites from the phylum Apicomplexa, such as Plasmodium and Toxoplasma. Both parasites, which are transmitted by mosquitoes and cats, have an enormous impact on global heath. Plasmodium causes 228 million malaria infections and around 400 000 deaths per year. Toxoplasma, which infects even one third of the human population, can cause severe symptoms in some people, and is particularly dangerous during pregnancy.

Read more on the DESY PETRA III website

Image: Molecular structure of essential light chain (ELC) protein in Plasmodium glideosome. Blue represents the electron density of the protein, with bonds between atoms indicated in yellow and water molecules indicated in red. The crystal structure at a resolution of 1.5 Ångström (0.15 millionths of a millimetre) was obtained at the EMBL beamlines at DESY’S X-ray source PETRA III. Credit: EMBL, Samuel Pazicky

Every moment of ultrafast chemical bonding now captured on film

2020/06/25

The emerging moment of bond formation, two separate bonding steps, and subsequent vibrational motions were visualized.

Targeted cancer drugs work by striking a tight bond between cancer cell and specific molecular targets that are involved in the growth and spread of cancer. Detailed images of such chemical bonding sites or pathways can provide key information necessary for maximizing the efficacy of oncogene treatments. However, atomic movements in a molecule
have never been captured in the middle of the action, not even for an extremely simple molecule such as a triatomic molecule, made of only three atoms. A research team led by IHEE Hyotcherl of the Institute for Basic Science (IBS, South Korea) (Professor, Department of Chemistry, KAIST), in collaboration with scientists at the Institute of Materials Structure Science of KEK (KEK IMSS, Japan), RIKEN (Japan) and Pohang Accelerator Laboratory (PAL, South Korea), reported the direct observation of the birthing moment of chemical bonds by tracking real-time atomic positions in the molecule. “We finally succeeded in capturing the ongoing reaction process of the chemical bond formation in the gold trimer. The femtosecond-resolution images revealed that such molecular events
took place in two separate stages, not simultaneously as previously assumed,” says Associate Director IHEE Hyotcherl, the corresponding author of the study. “The atoms in the gold trimer complex atoms remain in motion even after the chemical bonding is complete. The
distance between the atoms increased and decreased periodically, exhibiting the molecular vibration. These visualized molecular vibrations allowed us to name the characteristic motion of each observed vibrational mode.” adds Ihee.

>Read more on the KEK (Photon Factory) website

Image: Figure 2. (left) Time-dependent positions of the wave packet in the multidimensional nuclear coordinates were obtained from the femtosecond x-ray scattering experiment on a gold trimer complex. (Credit: Nature & IBS) (right) By inspecting the motion of the wave packet, it was revealed that the bond formation reaction in the gold trimer complex occurs through an asynchronous bond formation mechanism. (Yellow: gold atoms, gray: carbon atom, blue: nitrogen atom, 1000 times 1 fs is 1 picosecond (ps), 1000 times 1 ps is 1 nanosecond (ns))

Credit: KEK IMSS

First megahertz rate timing jitter observed

2020/06/17

A report published today in the Journal Optica demonstrates accurate synchronisation of optical and X-ray lasers crucial for pump-probe experiments at XFEL. These snapshots taken during a reaction are stitched together to make molecular movies.

One of the ultimate goals for scientists using state-of-the-art X-ray free-electron lasers such as European XFEL is to be able to film the details of chemical and biological reactions. By stitching together a series of snapshots taken at different time intervals during a reaction, a molecular movie can be made of the process. So called pump-probe experiments use a precisely synchronised optical laser to trigger a reaction (the ‘pump’), while the X-ray laser takes a snapshot of the molecular structure at defined times during the reaction (the ‘probe’).

European XFEL now generates the ultrafast and ultra-intense light pulses needed to capture these processes that occur on extremely short timescales. The pulses of X-ray light generated by European XFEL are each less than a few millionths of a billionth of a second, or a few femtoseconds – fast enough to capture the series of events in a biological or chemical reaction. An accurate synchronization of the X-ray and optical laser pulses at these timescales is, however, challenging. Furthermore, tiny variations in the alignment and path travelled by the laser pulses caused, for example, by fluctuations in air pressure, or expansion in the electrical cables, have a relatively large impact on the accuracy of this experimental set-up. This variation is known as ‘timing jitter’. For pump-probe experiments to be successful, the jitter must be kept to a minimum, and be accurately characterized so that scientists can take it into account when assessing their data.

Read more on the European XFEL website
Image : The XPB/SFX instrument at European XFEL.

Credit: European XFEL / Jan Hosan

Crystals, lasers, glasses, and bent molecules: adventures in nonlinear optics

2020/04/222020/04/22

Light is an indispensable scientific tool. For example, laser-based optical sensors can detect oxygen in the environment, proteins in biomedical samples, and process markers in industrial settings, among other applications. However, not all wavelengths of light can be generated by a single laser, which limits what chemicals can be detected with optical sensing. That’s where nonlinear optical crystals can help. By shining multiple lasers with different wavelengths through such crystals, researchers can tune laser beams via frequency conversion and cover more of the optical spectra. This has been a successful approach for wavelengths from ultraviolet to near-infrared(IR), but the mid-IR region has lacked practical nonlinear optical crystals. However, crystals may not be the only game in town. A multi-institution international research team is exploring a possible solution to the crystal problem: cutting-edge glasses containing mercuric iodide. The idea is that these glasses could behave like nonlinear optical crystals, offering an enticing approach to the generation of novel amorphous optical materials. But first, the researchers needed to figure out what these glasses look like at the atomic scale. For that, they went to the U.S. Department of Energy’s (DOE’s) Advanced Photon Source (APS) to collect high-energy x-ray diffraction data. By combining the diffraction data with other structural data and computer modeling, the team uncovered the secrets behind how a glass can act like a crystal.

Nonlinear optical crystals are widely used in photonics applications, but can be challenging to synthesize. To sidestep the need for crystals, scientists have been pursuing glassy materials that can tune lasers. One challenge is that glassy materials with isotropic internal structures aren’t able to perform the frequency conversion necessary to tune lasers. However, glasses with chiral asymmetric properties have nonlinear optical potential. This research team is investigating hybrid molecular/network glasses with non-centrosymmetric mercuric iodide (HgI₂).

Image: Schematic representation of second harmonic generation as light passes through bent HgI2 molecules adopting a non-random orientation within mesoscopic domains of sulfide glass.

Plastic from Wood

2020/02/272020/02/27

X-ray analysis points the way to lignin-based components made to measure

The biopolymer lignin is a by-product of papermaking and a promising raw material for manufacturing sustainable plastic materials. However, the quality of this naturally occurring product is not as uniform as that of petroleum-based plastics. An X-ray analysis carried out at DESY reveals for the first time how the internal molecular structure of different lignin products is related to the macroscopic properties of the respective materials. The study, which has been published in the journal Applied Polymer Materials, provides an approach for a systematic understanding of lignin as a raw material to allow for production of lignin-based bioplastics with different properties, depending on the specific application.

Image: Lignin is a promising raw material (left) for thermoplast (right) production.
Credit: KTH Stockholm, Marcus Jawerth

Watching complex molecules at work

2020/01/142020/01/15

A new method of infrared spectroscopy developed at BESSY II makes single-measurement observation and analysis of very fast as well as irreversible reaction mechanisms in molecules feasible for the first time.

Previously, thousands of such reactions have had to be run and measured for this purpose. The research team has now used the new device to investigate how rhodopsin molecules change after activation by light – a process that is the basis of how we see.

Time-resolved infrared spectroscopy in the sub-millisecond range is an important method for studying the relationship between function and structure in biological molecules. However, the method only works if the reaction can be repeated many thousands of times. This is not the case for a large number of biological processes, though, because they often are based on very rapid and irreversible reactions, for example in vision. Individual light quanta entering the rods of the retina activate the rhodopsin protein molecules, which then decay after fulfilling their phototransductionfunction.

Image: Rhodopsin before (left) and after activation by light (right): The activation causes changes in functional groups inside the molecule (magnifying glass), which affect the entire molecule.
Credit: E. Ritter/HZB

First molecular movies at European XFEL

2019/11/182019/11/19

Scientists show how to use extremely short X-ray pulses to make the first movies of molecular processes at the European XFEL.

In a paper published today in Nature Methods, scientists show how to effectively use the high X-ray pulse repetition rate of the European XFEL to produce detailed molecular movies. This type of information can help us to better understand, for example, how a drug molecule reacts with proteins in a human cell, or how plant proteins store light energy.

Traditional structural biology methods use X-rays to produce snapshots of the 3D structure of molecules such as proteins. Although valuable, this information does not reveal details about the dynamics of biomolecular processes. If several snapshots can be taken in fast enough succession, however, these can be pasted together to make a so-called molecular movie. The high repetition rate of the extremely short X-ray pulses produced by the European XFEL makes it now possible to collect large amounts of data to produce movies with more frames than ever before. An international group of scientists have now worked out how to make optimal use of the European XFEL’s very high X-ray repetition rate to make these molecular movies at the facility in order to reveal unprecedented details of our world.

>Read more on the European XFEL website

Image: Artistic visualisation of a serial crystallography experiment. A stream of crystalline proteins are struck by an optical laser that initiates a reaction. Following a short delay the X-ray laser strikes the crystals. The information recorded about the arrangement of the atoms in the protein is used to reconstruct a model of the structure of the protein.
Credit: European XFEL / Blue Clay Studios

Breaking up buckyballs is hard to do

2019/09/242019/10/03

A new study shows how soccer ball-shaped molecules burst more slowly than expected when blasted with an X-ray laser beam.

As reported in Nature Physics, an international research team observed how soccer ball-shaped molecules made of carbon atoms burst in the beam of an X-ray laser. The molecules, called buckminsterfullerenes – buckyballs for short – consist of 60 carbon atoms arranged in alternating pentagons and hexagons like the leather coat of a soccer ball. These molecules were expected to break into fragments after being bombarded with photons, but the researchers watched in real time as buckyballs resisted the attack and delayed their break-up.

The team was led by Nora Berrah, a professor at the University of Connecticut, and included researchers from the Department of Energy’s SLAC National Accelerator Laboratory and the Deutsches Elektronen-Synchrotron (DESY) in Germany. The researchers focused their attention on examining the role of chemical effects, such as chemical bonds and charge transfer, on the buckyball’s fragmentation.

Using X-ray laser pulses from SLAC’s Linac Coherent Light Source (LCLS), the team showed how the bursting process, which takes only a few hundred femtoseconds, or millionths of a billionth of a second, unfolds over time. The results will be important for the analysis of sensitive proteins and other biomolecules, which are also frequently studied using bright X-ray laser flashes, and they also strengthen confidence in protein analysis with X-ray free-electron lasers (XFELs).

Image: An illustration shows how soccer ball-shaped molecules called buckyballs ionize and break up when blasted with an X-ray laser. A team of experimentalists and theorists identified chemical bonds and charge transfers as crucial factors that significantly delayed the fragmentation process by about 600 millionths of a billionth of a second.
Credit: Greg Stewart/SLAC National Accelerator Laboratory

For additional information: article published on the DESY website

Understanding the viruses that kill cancer cells

2019/04/122019/04/16

Taking inspiration from virology to find better treatments for cancer

There are some viruses, called oncolytic viruses, that can be trained to target and kill cancer cells. Scientists in the field of oncolytics want to engineer these viruses to make them safer and more effective so they can be used to treat more people and different types of cancers. To achieve this, they first have to fully understand at the molecular level all the different ways that the virus has evolved to infect healthy cells and cause disease. A research team from Cardiff University set out to better understand how a protein on the surface of a virus often used to kill cancer, called an adenovirus, binds to human cells to cause an infection. Using X-ray crystallography, the team was able to determine the structure of one the key adenovirus proteins. Using this information and after extensive computational analysis, the research team realised the virus was not binding the receptor on the cells that was originally thought. This has important implications for the development of new virotherapies and engineering of viruses to treat cancer. The more thoroughly the researchers can understand how the adenoviruses interact with cancer cells at the molecular level, the more safe and effective treatments can be brought to clinical trial in the future.

Getting the timing right for molecular movies

2019/04/022019/04/04

Jitter effects measured at European XFEL

Scientists have long dreamed of being able to film the details of chemical and biological reactions by taking, and stitching together snapshots of these processes. Getting the timing of the individual shots of the movies just right is dependent on a number of factors including understanding the timing variation, or so-called ‘jitter’, of the laser beams used to take the images. In an experiment published now in the journal Optics Letters, scientists describe how they measured the jitter at the SPB/SFX instrument at European XFEL and demonstrate how this unavoidable and undesirable effect might be overcome. The knowledge gained from these movies could lead to new technological innovations and developments.
Biological and chemical reactions happen extremely quickly and filming them requires an extremely fast and precise camera. Much like a fast exposure time can be used to capture a series of images showing details of the movements a sprinter makes during a race, so the extremely short bursts of X-rays produced by facilities such as European XFEL are short and frequent enough to capture the sequence of molecular movements that happen during a reaction. To make a molecular movie, scientists can, for example, first kick-start the reaction they want to film by hitting their sample of choice with a laser. Then, the intense X-ray laser is used to take a sequence of images of the molecular process as it unfolds. Getting the timing of the two lasers just right is crucial for the success of these types of experiments, however, at these speeds, it is not trivial.

>Read more on the European XFEL website
Image: The SPB/SFX instrument at European XFEL.
Credit: European XFEL

Clear view of “Robo” neuronal receptor opens door for new cancer drugs

2019/03/072019/03/12

During brain development, billions of neuron nerve cells must find accurate pathways in the brain in order to form trillions of neuronal circuits enabling us to enjoy cognitive, sensory and emotional wellbeing.

To achieve this remarkable precision, migrating neurons use special protein receptors that sense the environment around them and guide the way so these neurons stay on the right path. In a new study published in Cell, researchers from Bar-Ilan University and Tel Aviv University in Israel, EMBL Grenoble in France and University of Exeter in the UK report on their discovery of the intricate molecular mechanism that allows a key guidance receptor, “Robo”, to react to signals in its environment.

One of the most important protein signaling systems that guide neurons consists of the cell surface receptor “Robo” and its external guidance cue, “Slit”. “Slit and Robo can be identified in virtually all animals with a nervous system, from a 1 mm-long nematode all the way to humans,” explains researcher Yarden Opatowsky, associate professor and head of the Laboratory of Structural Biology at Bar-Ilan University and who led the research.

Image: A surface representation of the crystal structure of the extracellular portion of human Robo2. The yellow region represents the domain where dimerisation takes place. Here, we see it blocked by the other domains, meaning dimerisation cannot take place and that Robo2 is inactivated.
Credit: Y. Opatowsky.

What keeps spiders on the ceiling?

2019/02/042019/02/26

DESYs X-ray source PETRA III reveals details of adhesive structures of spider legs

Hunting spiders easily climb vertical surfaces or move upside down on the ceiling. A thousand tiny hairs at the ends of their legs make sure they do not fall off. Like the spider’s exoskeleton, these bristle-like hairs (so-called setae) mainly consist of proteins and chitin, which is a polysaccharide. To find out more about their fine structure, an interdisciplinary research team from the Biology and Physics departments at Kiel University and the Helmholtz-Zentrum Geesthacht (HZG) examined the molecular structure of these hairs in closer detail at DESY’s X-ray light source PETRA III and at the European Synchrotron Radiation Facility ESRF. Thanks to the highly energetic X-ray light, the researchers discovered that the chitin molecules of the setae are specifically arranged to withstand the stresses of constant attachment and detachment. Their findings could be the basis for highly resilient future materials. They have been published in the current issue of the Journal of the Royal Society Interface.

Image: In order to find out why the hunting spider Cupiennius salei adheres so well to vertical surfaces, the interdisciplinary research team investigates the tiny adhesive hairs on the spider legs.
Credit: Universität Kiel, Julia Siekmann

Steering the outcome of photoionization in a molecule

2018/10/152018/10/25

An important step towards the understanding and control of photoinduced fragmentation processes in molecules has been achieved in an experiment on the H₂ molecule taking advantage of the unique properties of the FERMI free-electron laser source in the vacuum ultraviolet (VUV) photon energy range.
Molecular dissociation, i.e., the breaking of a chemical bond, is governed by the coupling of electronic and nuclear motion and, once understood and controlled in large systems, e.g., by utilizing ultrashort light pulses, has the potential to impact tremendously photochemical and biochemical applications. A team of both experimentalists and theoreticians from France (CNRS, Université Paris-Sud, Université de Bordeaux), Spain (Universidad Autónoma de Madrid), Germany (European XFEL), and Italy (Elettra-Sincrotrone Trieste) has demonstrated that the outcome of dissociative (DI) and nondissociative (NDI) photoionization in the simplest of all molecules, H₂, can be controlled exploiting nonlinear two-photon ionization with intense femtosecond pulses in the VUV.
The FERMI seeded free-electron laser is currently the only light source worldwide that provides external users access to bright femtosecond pulses at wavelengths in the VUV up to 100 nm, the energy regime required for studying nonlinear two-photon single-ionization in H₂. The high spectral resolution and precise tunability of the 100-fs pulses provided by FERMI made it possible to selectively excite single vibrational levels in the neutral intermediate B state of H₂ (blue line in Fig. 1). Absorption of a second VUV photon then leads to NDI or DI into the ionic H₂⁺ ground state (green in Fig. 1) or to DI into the first excited H₂⁺2p continuum (orange in Fig. 1). In single-photon single-ionization of H₂, the yield of DI is very low – less than 2%. By contrast, recent ab initiocalculations suggest that the ratio of DI/NDI can be increased significantly in resonance-enhanced two-photon ionization and that it can be controlled by varying the pulse duration between 2 and 10 fs.

>Read more on the Elettra website

Image: (a) Schematic of resonant two-photon ionization viathe B intermediate state (12.51 eV). The grey shaded area shows the Franck-Condon region for one-photon absorption from the H2electronic ground state. The dashed purple arrows visualize the range for the absorption of the second FEL photon. The green (red) horizontal line shows the ionization threshold at 15.43 eV (dissociation limit at 18.08 eV). (b) The experimental photoelectron spectrum shows a clear separation of electrons correlated to NDI and DI. For DI, it is close to the prediction of the Condon-reflection approximation, i.e., the projection of the vibrational wavefunction onto the dissociative 2p continuum state. The infinite-time limit calculation (grey line for the convolution of the contributions from the two first ionization continua) reproduces the main features of the spectrum. The differences between experiment and calculation indicates that at FERMI a timescale between ultrafast dynamics and steady-state excitation is probed.

Snaphot of molecular mechanism at work in lethal virus

2018/09/13

X-ray crystallography at the Australian Synchrotron contributed to major research findings.

Data collected on the macromolecular crystallography beamlines at the Australian Synchrotron has contributed to major research findings on two deadly viruses, Hendra and Nipah, found in Australia, Asia and Africa. The viruses can be transmitted to humans not directly by the bat which is the natural carrier but by an infected animal like horses or pigs.

Beamline scientist, Dr David Aragao (pictured above), a co-author on the paper in Nature Communications, said that obtaining a clear motion picture of key biological process at the molecular level of viruses is often not available with current biomedical techniques.
“However, using X-ray crystallography from data collected on both MX1 and MX2 beamlines at the Australian Synchrotron, we were able to obtain 8 ‘photograph-like’ snapshots of the molecular process that allows the Hendra and Nipah virus to replicate.“

Two authors of the paper, PhD students Kate Smith and Sofiya Tsimbalyuk, who are co-supervised by Aragao and his collaborator Professor of Biochemistry Jade Forwood of the Graham Centre for Agricultural Innovation Charles Sturt University, used the Synchrotron extensively collecting multiple data sets that required extensive refinements over two years to isolate the mechanism of interest.

Image: Beamline scientist, Dr David Aragao.