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Dive into the research topics where Andrew Aquila is active.

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Featured researches published by Andrew Aquila.


Nature | 2011

Femtosecond x-ray protein nanocrystallography

Henry N. Chapman; Petra Fromme; Anton Barty; Thomas A. White; Richard A. Kirian; Andrew Aquila; Mark S. Hunter; Joachim Schulz; Daniel P. DePonte; Uwe Weierstall; R. Bruce Doak; Filipe R. N. C. Maia; Andrew V. Martin; Ilme Schlichting; Lukas Lomb; Nicola Coppola; Robert L. Shoeman; Sascha W. Epp; Robert Hartmann; Daniel Rolles; A. Rudenko; Lutz Foucar; Nils Kimmel; Georg Weidenspointner; Peter Holl; Mengning Liang; Miriam Barthelmess; Carl Caleman; Sébastien Boutet; Michael J. Bogan

X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction ‘snapshots’ are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (∼200 nm to 2 μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.


Nature | 2011

Single mimivirus particles intercepted and imaged with an X-ray laser

M. Marvin Seibert; Tomas Ekeberg; Filipe R. N. C. Maia; Martin Svenda; Jakob Andreasson; O Jonsson; Duško Odić; Bianca Iwan; Andrea Rocker; Daniel Westphal; Max F. Hantke; Daniel P. DePonte; Anton Barty; Joachim Schulz; Lars Gumprecht; Nicola Coppola; Andrew Aquila; Mengning Liang; Thomas A. White; Andrew V. Martin; Carl Caleman; Stephan Stern; Chantal Abergel; Virginie Seltzer; Jean-Michel Claverie; Christoph Bostedt; John D. Bozek; Sébastien Boutet; A. Miahnahri; Marc Messerschmidt

X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions. Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma. The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval. Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source. Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000 K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.


Science | 2012

High-resolution protein structure determination by serial femtosecond crystallography

Sébastien Boutet; Lukas Lomb; Garth J. Williams; Thomas R. M. Barends; Andrew Aquila; R. Bruce Doak; Uwe Weierstall; Daniel P. DePonte; Jan Steinbrener; Robert L. Shoeman; Marc Messerschmidt; Anton Barty; Thomas A. White; Stephan Kassemeyer; Richard A. Kirian; M. Marvin Seibert; Paul A. Montanez; Chris Kenney; R. Herbst; P. Hart; J. Pines; G. Haller; Sol M. Gruner; Hugh T. Philipp; Mark W. Tate; Marianne Hromalik; Lucas J. Koerner; Niels van Bakel; John Morse; Wilfred Ghonsalves

Size Matters Less X-ray crystallography is a central research tool for uncovering the structures of proteins and other macromolecules. However, its applicability typically requires growth of large crystals, in part because a sufficient number of molecules must be present in the lattice for the sample to withstand x-ray—induced damage. Boutet et al. (p. 362, published online 31 May) now demonstrate that the intense x-ray pulses emitted by a free-electron laser source can yield data in few enough exposures to uncover the high-resolution structure of microcrystals. A powerful x-ray laser source can probe proteins in detail using much smaller crystals than previously required. Structure determination of proteins and other macromolecules has historically required the growth of high-quality crystals sufficiently large to diffract x-rays efficiently while withstanding radiation damage. We applied serial femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals (less than 1 micrometer by 1 micrometer by 3 micrometers) of the well-characterized model protein lysozyme. The agreement with synchrotron data demonstrates the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.


Science | 2013

Natively Inhibited Trypanosoma brucei Cathepsin B Structure Determined by Using an X-ray Laser

Karol Nass; Daniel P. DePonte; Thomas A. White; Dirk Rehders; Anton Barty; Francesco Stellato; Mengning Liang; Thomas R. M. Barends; Sébastien Boutet; Garth J. Williams; Marc Messerschmidt; M. Marvin Seibert; Andrew Aquila; David Arnlund; Sasa Bajt; Torsten Barth; Michael J. Bogan; Carl Caleman; Tzu Chiao Chao; R. Bruce Doak; Holger Fleckenstein; Matthias Frank; Raimund Fromme; Lorenzo Galli; Ingo Grotjohann; Mark S. Hunter; Linda C. Johansson; Stephan Kassemeyer; Gergely Katona; Richard A. Kirian

Diffraction Before Destruction A bottleneck in x-ray crystallography is the growth of well-ordered crystals large enough to obtain high-resolution diffraction data within an exposure that limits radiation damage. Serial femtosecond crystallography promises to overcome these constraints by using short intense pulses that out-run radiation damage. A stream of crystals is flowed across the free-electron beam and for each pulse, diffraction data is recorded from a single crystal before it is destroyed. Redecke et al. (p. 227, published online 29 November; see the Perspective by Helliwell) used this technique to determine the structure of an enzyme from Trypanosoma brucei, the parasite that causes sleeping sickness, from micron-sized crystals grown within insect cells. The structure shows how this enzyme, which is involved in degradation of host proteins, is natively inhibited prior to activation, which could help in the development of parasite-specific inhibitors. In vivo crystallization and serial femtosecond crystallography reveal the structure of a sleeping sickness parasite protease. [Also see Perspective by Helliwell] The Trypanosoma brucei cysteine protease cathepsin B (TbCatB), which is involved in host protein degradation, is a promising target to develop new treatments against sleeping sickness, a fatal disease caused by this protozoan parasite. The structure of the mature, active form of TbCatB has so far not provided sufficient information for the design of a safe and specific drug against T. brucei. By combining two recent innovations, in vivo crystallization and serial femtosecond crystallography, we obtained the room-temperature 2.1 angstrom resolution structure of the fully glycosylated precursor complex of TbCatB. The structure reveals the mechanism of native TbCatB inhibition and demonstrates that new biomolecular information can be obtained by the “diffraction-before-destruction” approach of x-ray free-electron lasers from hundreds of thousands of individual microcrystals.


Optics Express | 2012

Time-resolved protein nanocrystallography using an X-ray free-electron laser

Andrew Aquila; Mark S. Hunter; R. Bruce Doak; Richard A. Kirian; Petra Fromme; Thomas A. White; Jakob Andreasson; David Arnlund; Sasa Bajt; Thomas R. M. Barends; Miriam Barthelmess; Michael J. Bogan; Christoph Bostedt; Hervé Bottin; John D. Bozek; Carl Caleman; Nicola Coppola; Jan Davidsson; Daniel P. DePonte; Veit Elser; Sascha W. Epp; Benjamin Erk; Holger Fleckenstein; Lutz Foucar; Matthias Frank; Raimund Fromme; Heinz Graafsma; Ingo Grotjohann; Lars Gumprecht; Janos Hajdu

We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.


Science | 2015

Direct observation of ultrafast collective motions in CO myoglobin upon ligand dissociation

Thomas R. M. Barends; Lutz Foucar; Albert Ardevol; Karol Nass; Andrew Aquila; Sabine Botha; R. Bruce Doak; Konstantin Falahati; Elisabeth Hartmann; M. Hilpert; Marcel Heinz; Matthias C. Hoffmann; Jürgen Köfinger; Jason E. Koglin; Gabriela Kovácsová; Mengning Liang; Despina Milathianaki; Henrik T. Lemke; Jochen Reinstein; C.M. Roome; Robert L. Shoeman; Garth J. Williams; Irene Burghardt; Gerhard Hummer; Sébastien Boutet; Ilme Schlichting

Observing ultrafast myoglobin dynamics The oxygen-storage protein myoglobin was the first to have its three-dimensional structure determined and remains a workhorse for understanding how protein structure relates to function. Barends et al. used x-ray free-electron lasers with femtosecond short pulses to directly observe motions that occur within half a picosecond of CO dissociation (see the Perspective by Neutze). Combining the experiments with simulations shows that ultrafast motions of the heme couple to subpicosecond protein motions, which in turn couple to large-scale motions. Science, this issue p. 445, see also p. 381 Time-resolved crystallography at an x-ray laser reveals ultrafast structural changes in myoglobin upon ligand dissociation. [Also see Perspective by Neutze] The hemoprotein myoglobin is a model system for the study of protein dynamics. We used time-resolved serial femtosecond crystallography at an x-ray free-electron laser to resolve the ultrafast structural changes in the carbonmonoxy myoglobin complex upon photolysis of the Fe-CO bond. Structural changes appear throughout the protein within 500 femtoseconds, with the C, F, and H helices moving away from the heme cofactor and the E and A helices moving toward it. These collective movements are predicted by hybrid quantum mechanics/molecular mechanics simulations. Together with the observed oscillations of residues contacting the heme, our calculations support the prediction that an immediate collective response of the protein occurs upon ligand dissociation, as a result of heme vibrational modes coupling to global modes of the protein.


Nature Methods | 2012

In vivo protein crystallization opens new routes in structural biology

Rudolf Koopmann; Karolina Cupelli; Karol Nass; Daniel P. DePonte; Thomas A. White; Francesco Stellato; Dirk Rehders; Mengning Liang; Jakob Andreasson; Andrew Aquila; Sasa Bajt; Miriam Barthelmess; Anton Barty; Michael J. Bogan; Christoph Bostedt; Sébastien Boutet; John D. Bozek; Carl Caleman; Nicola Coppola; Jan Davidsson; R. Bruce Doak; Tomas Ekeberg; Sascha W. Epp; Benjamin Erk; Holger Fleckenstein; Lutz Foucar; Heinz Graafsma; Lars Gumprecht; J. Hajdu; Christina Y. Hampton

Protein crystallization in cells has been observed several times in nature. However, owing to their small size these crystals have not yet been used for X-ray crystallographic analysis. We prepared nano-sized in vivo–grown crystals of Trypanosoma brucei enzymes and applied the emerging method of free-electron laser-based serial femtosecond crystallography to record interpretable diffraction data. This combined approach will open new opportunities in structural systems biology.


Nature Methods | 2012

Lipidic phase membrane protein serial femtosecond crystallography.

Linda C. Johansson; David Arnlund; Thomas A. White; Gergely Katona; Daniel P. DePonte; Uwe Weierstall; R. Bruce Doak; Robert L. Shoeman; Lukas Lomb; Erik Malmerberg; Jan Davidsson; Karol Nass; Mengning Liang; Jakob Andreasson; Andrew Aquila; Sasa Bajt; Miriam Barthelmess; Anton Barty; Michael J. Bogan; Christoph Bostedt; John D. Bozek; Carl Caleman; Ryan Coffee; Nicola Coppola; Tomas Ekeberg; Sascha W. Epp; Benjamin Erk; Holger Fleckenstein; Lutz Foucar; Heinz Graafsma

X-ray free electron laser (X-FEL)-based serial femtosecond crystallography is an emerging method with potential to rapidly advance the challenging field of membrane protein structural biology. Here we recorded interpretable diffraction data from micrometer-sized lipidic sponge phase crystals of the Blastochloris viridis photosynthetic reaction center delivered into an X-FEL beam using a sponge phase micro-jet.


Nature | 2012

Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight

N. D. Loh; Christina Y. Hampton; Andrew V. Martin; Dmitri Starodub; Raymond G. Sierra; A. Barty; Andrew Aquila; Joachim Schulz; Lukas Lomb; Jan Steinbrener; Robert L. Shoeman; Stephan Kassemeyer; Christoph Bostedt; John D. Bozek; Sascha W. Epp; Benjamin Erk; Robert Hartmann; Daniel Rolles; A. Rudenko; Benedikt Rudek; Lutz Foucar; Nils Kimmel; Georg Weidenspointner; G. Hauser; Peter Holl; Emanuele Pedersoli; Mengning Liang; M. M. Hunter; Lars Gumprecht; Nicola Coppola

The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology to climate science, yet these properties are surprisingly difficult to measure in the particles’ native environment. Electron microscopy requires collection of particles on a substrate; visible light scattering provides insufficient resolution; and X-ray synchrotron studies have been limited to ensembles of particles. Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins, vibrational energy transfer by the hydrodynamic interaction of amino acids, and large-scale production of nanoscale structures by flame synthesis.


Physical Review Letters | 2014

X-Ray Diffraction from Isolated and Strongly Aligned Gas-Phase Molecules with a Free-Electron Laser

Jochen Küpper; Stephan Stern; Lotte Holmegaard; Frank Filsinger; Arnaud Rouzée; Artem Rudenko; Per Johnsson; Andrew V. Martin; Marcus Adolph; Andrew Aquila; Sasa Bajt; Anton Barty; Christoph Bostedt; John D. Bozek; Carl Caleman; Ryan Coffee; Nicola Coppola; Tjark Delmas; Sascha W. Epp; Benjamin Erk; Lutz Foucar; Tais Gorkhover; Lars Gumprecht; Andreas Hartmann; Robert Hartmann; Günter Hauser; Peter Holl; André Hömke; Nils Kimmel; Faton Krasniqi

We report experimental results on x-ray diffraction of quantum-state-selected and strongly aligned ensembles of the prototypical asymmetric rotor molecule 2,5-diiodobenzonitrile using the Linac Coherent Light Source. The experiments demonstrate first steps toward a new approach to diffractive imaging of distinct structures of individual, isolated gas-phase molecules. We confirm several key ingredients of single molecule diffraction experiments: the abilities to detect and count individual scattered x-ray photons in single shot diffraction data, to deliver state-selected, e.g., structural-isomer-selected, ensembles of molecules to the x-ray interaction volume, and to strongly align the scattering molecules. Our approach, using ultrashort x-ray pulses, is suitable to study ultrafast dynamics of isolated molecules.

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Anton Barty

Lawrence Livermore National Laboratory

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Mengning Liang

SLAC National Accelerator Laboratory

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Sébastien Boutet

SLAC National Accelerator Laboratory

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Sasa Bajt

Lawrence Livermore National Laboratory

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John D. Bozek

SLAC National Accelerator Laboratory

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Christoph Bostedt

Argonne National Laboratory

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