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Exploration of structure-activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment linking and active learning

28 May 2025 | BioXFEL Publications | Contributor(s): Galen J. Correy, Moira M. Rachman, Takaya Togo, Stefan Gahbauer, Yagmur U. Doruk, Maisie G. V. Stevens, Priyadarshini Jaishankar, Brian Kelley, Brian Goldman, Molly Schmidt, Trevor Kramer, Dmytro S. Radchenko, Yurii S. Moroz, Alan Ashworth, Patrick Riley, Brian K. Shoichet, Adam R. Renslo, W. Patrick Walters, James Fraser

https://doi.org/10.1126/sciadv.ads7187 The macrodomain of severe acute respiratory syndrome coronavirus 2 nonstructural protein 3 is required for viral pathogenesis and is an emerging antiviral target. We previously performed an x-ray crystallography–based fragment screen and found …

Advances in microfluidic mixers for time-resolved structural biology with X-rays

23 May 2025 | BioXFEL Publications | Contributor(s): Kara Zielinski, Lois Pollack

https://doi.org/10.1007/s12551-025-01321-x journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Zielinski, K. A., & Pollack, L. (2025). Advances in microfluidic mixers for time-resolved structural biology with X-rays. Biophysical Reviews. https://doi.org/10.1007/s12551-025-01321-x Kara …

Where and how to house big data on small fragments

05 May 2025 | BioXFEL Publications | Contributor(s): Daniel A. Erlanson, Stephen K. Burley, Daren Fearon, James Fraser, Dale Kreitler, Maria Cristina Nonato, Naoki Sakai, Jan Wollenhaupt, Manfred S. Weiss

https://doi.org/10.1038/s41467-025-59233-z journal-article Erlanson, D. A., Burley, S. K., Fearon, D., Fraser, J. S., Kreitler, D., Nonato, M. C., Sakai, N., Wollenhaupt, J., & Weiss, M. S. (2025). Where and how to house big data on small fragments. Nature Communications, 16(1). …

Structures of myxobacterial phytochrome revealed by cryo-EM using the Spotiton technique and with x-ray crystallography

01 May 2025 | BioXFEL Publications | Contributor(s): Prabin Karki, David Menendez, William Budell, Shishir Dangi, Carolina Hernandez, Joshua Mendez, SRINIVASAN MUNIYAPPAN, Shibom Basu, Peter Schwander, Tek Narsingh Malla, Emina Stojkovic, Marius Schmidt

https://doi.org/10.1063/4.0000301 Phytochromes are red-light photoreceptors first identified in plants, with homologs found in bacteria and fungi, that regulate a variety of critical physiological processes. They undergo a reversible photocycle between two distinct states: a red-light-absorbing Pr …

Advances in uncovering the mechanisms of macromolecular conformational entropy

24 Apr 2025 | BioXFEL Publications | Contributor(s): Stephanie A. Wankowicz, James Fraser

https://doi.org/10.1038/s41589-025-01879-3 journal-article Wankowicz, S. A., & Fraser, J. S. (2025). Advances in uncovering the mechanisms of macromolecular conformational entropy. Nature Chemical Biology, 21(5), 623–634. https://doi.org/10.1038/s41589-025-01879-3 Stephanie A. Wankowicz and …

Characterizing single-stranded RNA using SAXS and single-molecule FRET

10 Apr 2025 | BioXFEL Publications | Contributor(s): Scout Fronhofer, Tong Wang, Lois Pollack

https://doi.org/10.1063/4.0000644 Single-stranded RNA molecules play many important roles in biology, including in the formation of biomolecular condensates through liquid-liquid phase separation [1]. The flexibility of these molecules is critical, allowing them to take on a variety of …

Determining the Enzymatic Mechanism of DJ-1 Using a New Approach to Mix-and-Inject Synchrotron Serial Crystallography

10 Apr 2025 | BioXFEL Publications | Contributor(s): Kara Zielinski, Cole Dolamore, Kevin Dalton, Doeke Hekstra, Robert Henning, Vukica Srajer, Mark Wilson, Lois Pollack

https://doi.org/10.1063/4.0000425 Mix-and-inject serial crystallography (MISC) is a well established technique at X-ray Free Electron Lasers (XFELs) to capture snapshots of the progress of a reaction, typically between a protein and a ligand. Key to this method are specialized diffusive mixers …

Improving Cryo-EM Experimental Data Fit with Automated Multiconformer Modeling for Proteins and Non-proteins

10 Apr 2025 | BioXFEL Publications | Contributor(s): Stephanie Wankowicz, Jessica Flowers, Daniel Hogan, Ashraya Ravikumar, James Fraser

https://doi.org/10.1063/4.0000388 Biomolecules exchange between multiple conformational states in their folded state, crucial for their function. Traditional structural biology methods, such as X-ray crystallography and cryogenic electron microscopy (cryo-EM), produce density maps that are ensemble …

Determining the Mechanism of DJ-1 Using Mix-and-Inject Synchrotron Serial Crystallography

10 Apr 2025 | BioXFEL Publications | Contributor(s): Cole Dolamore, Kara Zielinski, Kevin Dalton, Stephen Meisburger, John Termini, Nathan Smith, Robert Henning, Vukica Srajer, Doeke Hekstra, Lois Pollack, Mark Wilson

https://doi.org/10.1063/4.0000378 Determining the molecular basis of enzyme catalytic activity is a central challenge in biochemistry. Time-resolved serial X-ray crystallography using X-ray free electron (XFELs) and synchrotron sources allows enzyme reactions to be observed in real time in a …

Time-resolved cryogenic electron tomography using mix-and-inject microfluidic devices

10 Apr 2025 | BioXFEL Publications | Contributor(s): Peter Dahlberg, Joey Yoniles, Jacob Summers, Kara Zielinski, Cali Antolini, Mayura Panjalingam, Stella Lisova, Frank Moss, Maximus Perna, Christopher Kupitz, Mark S. Hunter, Lois Pollack, Soichi Wakatsuki

https://doi.org/10.1063/4.0000362 Cryogenic electron tomography (cryo-ET) is the highest resolution three-dimensional imaging technique applicable to the life sciences, enabling sub-nanometer visualization of rapidly frozen biological specimens preserved in their near native states. The rapid …

Exploring interface dynamics in plastic bonded-explosives: synthesis, characterization, and neutron reflectometry

22 Mar 2025 | BioXFEL Publications | Contributor(s): Michael R. Bull, Matthew J. Herman, Erik B. Watkins, John D. Yeager, Michael P. Marquez, Alexander M. Long, D. Travis Carver, Robert Knepper, Tonya L. Kuhl

https://doi.org/10.1080/07370652.2025.2472650 journal-article Bull, M. R., Herman, M. J., Watkins, E. B., Yeager, J. D., Marquez, M. P., Long, A. M., Carver, D. T., Knepper, R., & Kuhl, T. L. (2025). Exploring interface dynamics in plastic bonded-explosives: synthesis, characterization, and …

Probing the high-pressure densification of amorphous silica nanomaterials using SBA-15: An investigation into the paradoxical nature of the first sharp diffraction peak

04 Mar 2025 | BioXFEL Publications | Contributor(s): Michael R. Bull, Rachel C. Huber, Ping Yu, Tanner J Finney, Noah Felvey, Paul Chow, Yuming Xiao, Tonya L. Kuhl, Erik B. Watkins

https://doi.org/10.1016/j.jnoncrysol.2025.123448 journal-article Bull, M. R., Huber, R. C., Yu, P., Finney, T. J., Felvey, N., Chow, P., Xiao, Y., Kuhl, T. L., & Watkins, E. B. (2025). Probing the high-pressure densification of amorphous silica nanomaterials using SBA-15: An investigation into …

BPS2025 - Unraveling the catalytic mechanism of the SARS-CoV-2 macrodomain ADP-ribosylhydrolase

13 Feb 2025 | BioXFEL Publications | Contributor(s): Rishav Mitra, Galen Correy, James Fraser

https://doi.org/10.1016/j.bpj.2024.11.2882 journal-article Mitra, R., Correy, G., & Fraser, J. (2025). BPS2025 - Unraveling the catalytic mechanism of the SARS-CoV-2 macrodomain ADP-ribosylhydrolase. Biophysical Journal, 124(3), 553a. https://doi.org/10.1016/j.bpj.2024.11.2882 Rishav Mitra and …

BPS2025 - Automated, efficient, and rigorous absolute binding free energy calculations

13 Feb 2025 | BioXFEL Publications | Contributor(s): Steven Ayoub, Tyler Luchko, Michael Barton, David Case

https://doi.org/10.1016/j.bpj.2024.11.1764 journal-article Ayoub, S., Luchko, T., Barton, M., & Case, D. A. (2025). BPS2025 - Automated, efficient, and rigorous absolute binding free energy calculations. Biophysical Journal, 124(3), 318a–319a. https://doi.org/10.1016/j.bpj.2024.11.1764 Steven …

BPS2025 - Molecular simulation with 3D-RISM: Using hybrid Monte Carlo for efficient sampling

13 Feb 2025 | BioXFEL Publications | Contributor(s): Noah C. Pishaki, Tyler Luchko, David Case

https://doi.org/10.1016/j.bpj.2024.11.1742 journal-article Pishaki, N. C., Luchko, T., & Case, D. A. (2025). BPS2025 - Molecular simulation with 3D-RISM: Using hybrid Monte Carlo for efficient sampling. Biophysical Journal, 124(3), 314a. https://doi.org/10.1016/j.bpj.2024.11.1742 Noah C. Pishaki …

BPS2025 - Computational modeling of magnesium ion solvation around Escherichia coli 70S ribosome using 3D reference interaction site model of molecular solvation

13 Feb 2025 | BioXFEL Publications | Contributor(s): Tiannah York Van Elslande, Felipe Silva Carvalho, David Case, Silvia Cavagnero, Tyler Luchko

https://doi.org/10.1016/j.bpj.2024.11.509 journal-article Van Elslande, T. Y., Carvalho, F. S., Case, D., Cavagnero, S., & Luchko, T. (2025). BPS2025 - Computational modeling of magnesium ion solvation around Escherichia coli 70S ribosome using 3D reference interaction site model of molecular …

BPS2025 - Disordered RNA conformations and nucleotide-specific dynamics within ribonucleoprotein condensates

13 Feb 2025 | BioXFEL Publications | Contributor(s): Tong Wang, Qingyue Hu, Scout Fronhofer, Lois Pollack

https://doi.org/10.1016/j.bpj.2024.11.476 journal-article Wang, T., Hu, Q., Fronhofer, S., & Pollack, L. (2025). BPS2025 - Disordered RNA conformations and nucleotide-specific dynamics within ribonucleoprotein condensates. Biophysical Journal, 124(3), 76a. …

Filling data analysis gaps in time-resolved crystallography by machine learning

21 Jan 2025 | BioXFEL Publications | Contributor(s): Justin Trujillo, Russell Fung, Madan Kumar Shankar, Peter Schwander, Ahmad Hosseinizadeh

https://doi.org/10.1063/4.0000280 There is a growing understanding of the structural dynamics of biological molecules fueled by x-ray crystallography experiments. Time-resolved serial femtosecond crystallography (TR-SFX) with x-ray Free Electron Lasers allows the measurement of ultrafast structural …

Implementation of simultaneous ultraviolet/visible and x-ray absorption spectroscopy with microfluidics

10 Jan 2025 | BioXFEL Publications | Contributor(s): Olivia McCubbin Stepanic, Christopher J. Pollock, Kara Zielinski, William Foschi, Derek B. Rice, Lois Pollack, Serena DeBeer

https://doi.org/10.1063/5.0218572 X-ray spectroscopies are uniquely poised to describe the geometric and electronic structure of metalloenzyme active sites under a wide variety of sample conditions. UV/Vis (ultraviolet/visible) spectroscopy is a similarly well-established technique that can …

The impact of library size and scale of testing on virtual screening

03 Jan 2025 | BioXFEL Publications | Contributor(s): Fangyu Liu, Olivier Mailhot, Isabella S. Glenn, Seth F. Vigneron, Violla Bassim, Xinyu Xu, Karla Fonseca-Valencia, Matthew S. Smith, Dmytro S. Radchenko, James Fraser, Yurii S. Moroz, John J. Irwin, Brian K. Shoichet

https://doi.org/10.1038/s41589-024-01797-w journal-article Liu, F., Mailhot, O., Glenn, I. S., Vigneron, S. F., Bassim, V., Xu, X., Fonseca-Valencia, K., Smith, M. S., Radchenko, D. S., Fraser, J. S., Moroz, Y. S., Irwin, J. J., & Shoichet, B. K. (2025). The impact of library size and scale of …

DefNEtTrp: An Iron Dual Chelator Approach for Anticancer Application

04 Dec 2024 | BioXFEL Publications | Contributor(s): Israel Rodriguez, Carmen Acosta, Christopher Nieves-Escobar, Estelle Strangmark, Oscar Claudio-Ares, Adriana I. Vargas Figueroa, Alexandra M. Soto-Millán, Aixa M. Orta-Rivera, Andrei V. Astashkin, Arthur Tinoco

https://doi.org/10.1021/jacsau.4c00774 journal-article Rodríguez, I., Acosta, C., Nieves-Escobar, C., Strangmark, E., Claudio-Ares, O., Vargas Figueroa, A. I., Soto-Millán, A. M., M. Orta-Rivera, A., Astashkin, A. V., & Tinoco, A. D. (2024). DefNEtTrp: An Iron Dual Chelator Approach for …

Comprehensive characterization of gas dynamic virtual nozzles for x-ray free-electron laser experiments

26 Nov 2024 | BioXFEL Publications | Contributor(s): Konstantinos Karpos, Sahba Zaare, Dimitra Manatou, Roberto C. Alvarez, Vivek Krishnan, Clint Ottmar, Jodi Gilletti, Aian Pableo, Diandra Doppler, Adil Ansari, Reza Nazari, Alexandra Ros, Richard Kirian

https://doi.org/10.1063/4.0000262 We introduce a hardware–software system for rapidly characterizing liquid microjets for x-ray diffraction experiments. An open-source python-based software package allows for programmatic and automated data collection and analysis. We show how jet speed, length, …

Exploiting fourth-generation synchrotron radiation for enzyme and photoreceptor characterization

22 Nov 2024 | BioXFEL Publications | Contributor(s): Tek Narsingh Malla, SRINIVASAN MUNIYAPPAN, David Menendez, Favour Ogukwe, Aleksandar N. Dale, Joseph D. Clayton, Dominique D. Weatherall, Prabin Karki, Shishir Dangi, Victoria Mandella, A. Andrew Pacheco, Emina Stojkovic, Samuel L. Rose, Julien Orlans, Shibom Basu, Daniele De Sanctis, Marius Schmidt

https://doi.org/10.1107/s2052252524010868 The upgrade of the European Synchrotron Radiation Facility (ESRF) in Grenoble, France to an Extremely Brilliant Source (EBS) is expected to enable time-resolved synchrotron serial crystallography (SSX) experiments with sub-millisecond time resolution. ID29 …

Scaling and merging time-resolved pink-beam diffraction with variational inference

08 Nov 2024 | BioXFEL Publications | Contributor(s): Kara Zielinski, Cole Dolamore, Harrison K. Wang, Robert W. Henning, Mark A. Wilson, Lois Pollack, Vukica Srajer, Doeke R. Hekstra, Kevin M. Dalton

https://doi.org/10.1063/4.0000269 Time-resolved x-ray crystallography (TR-X) at synchrotrons and free electron lasers is a promising technique for recording dynamics of molecules at atomic resolution. While experimental methods for TR-X have proliferated and matured, data analysis is often …

Sequence-dependent conformational preferences of disordered single-stranded RNA

29 Oct 2024 | BioXFEL Publications | Contributor(s): Tong Wang, Weiwei He, Suzette A. Pabit, Lois Pollack, Serdal Kirmizialtin

https://doi.org/10.1016/j.xcrp.2024.102264 journal-article Wang, T., He, W., Pabit, S. A., Pollack, L., & Kirmizialtin, S. (2024). Sequence-dependent conformational preferences of disordered single-stranded RNA. Cell Reports Physical Science, 5(11), 102264. …

Crystal structure of the 4-hydroxybutyryl-CoA synthetase (ADP-forming) from nitrosopumilus maritimus

21 Oct 2024 | BioXFEL Publications | Contributor(s): Jerome Johnson, Bradley B. Tolar, Bilge Tosun, Yasuo Yoshikuni, Christopher A. Francis, Soichi Wakatsuki, Hasan Demirci

https://doi.org/10.1038/s42003-024-06432-x AbstractThe 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle from ammonia-oxidizing Thaumarchaeota is currently considered the most energy-efficient aerobic carbon fixation pathway. The Nitrosopumilus maritimus 4-hydroxybutyryl-CoA synthetase …

Author Correction: Cation-induced intramolecular coil-to-globule transition in poly(ADP-ribose)

04 Oct 2024 | BioXFEL Publications | Contributor(s): Tong Wang, Kush Coshic, Mohsen Badiee, Maranda R. McDonald, Aleksei Aksimentiev, Lois Pollack, Anthony K. L. Leung

https://doi.org/10.1038/s41467-024-52865-7 journal-article Wang, T., Coshic, K., Badiee, M., McDonald, M. R., Aksimentiev, A., Pollack, L., & Leung, A. K. L. (2024). Author Correction: Cation-induced intramolecular coil-to-globule transition in poly(ADP-ribose). Nature Communications, 15(1). …

In situ counter-diffusion crystallization and long-term crystal preservation in microfluidic fixed targets for serial crystallography

25 Sep 2024 | BioXFEL Publications | Contributor(s): Zhongrui Liu, Kevin Gu, Megan Shelby, Debdyuti Roy, SRINIVASAN MUNIYAPPAN, Marius Schmidt, Sankar Raju Narayanasamy, Matthew Coleman, Matthias Frank, Tonya L. Kuhl

https://doi.org/10.1107/s1600576724007544 Compared with batch and vapor diffusion methods, counter diffusion can generate larger and higher-quality protein crystals yielding improved diffraction data and higher-resolution structures. Typically, counter-diffusion experiments are conducted in …

Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain

13 Sep 2024 | BioXFEL Publications | Contributor(s): Gabriella O Estevam, Edmond M Linossi, Christian B Macdonald, Carla A Espinoza, Jennifer M Michaud, Willow Coyote-Maestas, Eric A Collisson, Natalia Jura, James Fraser

https://doi.org/10.7554/elife.91619.3 MET is a receptor tyrosine kinase (RTK) responsible for initiating signaling pathways involved in development and wound repair. MET activation relies on ligand binding to the extracellular receptor, which prompts dimerization, intracellular phosphorylation, and …

Cation-induced intramolecular coil-to-globule transition in poly(ADP-ribose)

10 Sep 2024 | BioXFEL Publications | Contributor(s): Tong Wang, Kush Coshic, Mohsen Badiee, Maranda R. McDonald, Aleksei Aksimentiev, Lois Pollack, Anthony K. L. Leung

https://doi.org/10.1038/s41467-024-51972-9 journal-article Wang, T., Coshic, K., Badiee, M., McDonald, M. R., Aksimentiev, A., Pollack, L., & Leung, A. K. L. (2024). Cation-induced intramolecular coil-to-globule transition in poly(ADP-ribose). Nature Communications, 15(1). …

CrysFormer: Protein structure determination via Patterson maps, deep learning, and partial structure attention

14 Aug 2024 | BioXFEL Publications | Contributor(s): Tom Pan, Chen Dun, Shikai Jin, Mitchell Miller, Anastasios Kyrillidis, George Phillips

https://doi.org/10.1063/4.0000252 Determining the atomic-level structure of a protein has been a decades-long challenge. However, recent advances in transformers and related neural network architectures have enabled researchers to significantly improve solutions to this problem. These methods use …

Distinct conformational states enable transglutaminase 2 to promote cancer cell survival versus cell death

12 Aug 2024 | BioXFEL Publications | Contributor(s): Cody Aplin, Kara Zielinski, Suzette Pabit, Deborah Ogunribido, William P. Katt, Lois Pollack, Richard A. Cerione, Shawn K. Milano

https://doi.org/10.1038/s42003-024-06672-x AbstractTransglutaminase 2 (TG2) is a GTP-binding, protein-crosslinking enzyme that has been investigated as a therapeutic target for Celiac disease, neurological disorders, and aggressive cancers. TG2 has been suggested to adopt two conformational states …

Comprehensive encoding of conformational and compositional protein structural ensembles through the mmCIF data structure

01 Jul 2024 | BioXFEL Publications | Contributor(s): Stephanie A. Wankowicz, James Fraser

https://doi.org/10.1107/s2052252524005098 In the folded state, biomolecules exchange between multiple conformational states crucial for their function. However, most structural models derived from experiments and computational predictions only encode a single state. To represent biomolecules …

Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase

17 Jun 2024 | BioXFEL Publications | Contributor(s): Roberto Efraín Díaz, Andrew K Ecker, Galen J Correy, Pooja Asthana, Iris Diane Young, Bryan Faust, Michael Thompson, Ian B Seiple, Steven Van Dyken, Richard M Locksley, James Fraser

http://dx.doi.org/10.7554/elife.89918.3 Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian …

Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase

17 Jun 2024 | BioXFEL Publications | Contributor(s): Roberto Efraín Díaz, Andrew K Ecker, Galen J Correy, Pooja Asthana, Iris Diane Young, Bryan Faust, Michael Thompson, Ian B Seiple, Steven Van Dyken, Richard M Locksley, James Fraser

https://doi.org/10.7554/elife.89918.3 Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian …

Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage

24 May 2024 | BioXFEL Publications | Contributor(s): Jingyou Rao, Ruiqi Xin, Christian Macdonald, Matthew K. Howard, Gabriella O. Estevam, Sook Wah Yee, Mingsen Wang, James Fraser, Willow Coyote-Maestas, Harold Pimentel

http://dx.doi.org/10.1186/s13059-024-03279-7 AbstractDeep mutational scanning (DMS) measures the effects of thousands of genetic variants in a protein simultaneously. The small sample size renders classical statistical methods ineffective. For example, p-values cannot be correctly calibrated when …

Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage

24 May 2024 | BioXFEL Publications | Contributor(s): Jingyou Rao, Ruiqi Xin, Christian Macdonald, Matthew K. Howard, Gabriella O. Estevam, Sook Wah Yee, Mingsen Wang, James Fraser, Willow Coyote-Maestas, Harold Pimentel

https://doi.org/10.1186/s13059-024-03279-7 AbstractDeep mutational scanning (DMS) measures the effects of thousands of genetic variants in a protein simultaneously. The small sample size renders classical statistical methods ineffective. For example, p-values cannot be correctly calibrated when …

Developing mix-and-inject serial crystallography at synchrotrons

10 May 2024 | BioXFEL Publications | Contributor(s): K. A. Zielinski, L. Pollack

https://doi.org/10.1107/s2053273323090666 journal-article Zielinski, K. A., & Pollack, L. (2023). Developing mix-and-inject serial crystallography at synchrotrons. Acta Crystallographica Section A Foundations and Advances, 79(a2), C550–C550. https://doi.org/10.1107/s2053273323090666 K. A. …

Sugar ring alignment and dynamics underline cytarabine and gemcitabine inhibition on Pol η catalyzed DNA synthesis

10 May 2024 | BioXFEL Publications | Contributor(s): Caleb Chang, Grace Zhou, Christie Lee Luo, Sarah Eleraky, Madeline Moradi, Yang Gao

http://dx.doi.org/10.1016/j.jbc.2024.107361 journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Chang, C., Zhou, G., Lee Luo, C., Eleraky, S., Moradi, M., & Gao, Y. (2024). Sugar ring alignment and dynamics underline cytarabine and gemcitabine inhibition on Pol η catalyzed DNA …

Time-resolved cryogenic electron tomography for the study of transient cellular processes

08 May 2024 | BioXFEL Publications | Contributor(s): Joseph Yoniles, Jacob A. Summers, Kara Zielinski, Cali Antolini, Mayura Panjalingam, Stella Lisova, Frank R. Moss, Maximus Aldo Di Perna, Christopher Kupitz, Mark S. Hunter, Lois Pollack, Soichi Wakatsuki, Peter D. Dahlberg

http://dx.doi.org/10.1091/mbc.e24-01-0042 Cryogenic electron tomography (cryo-ET) is the highest resolution imaging technique applicable to the life sciences, enabling subnanometer visualization of specimens preserved in their near native states. The rapid plunge freezing process used to prepare …

Time-resolved cryogenic electron tomography for the study of transient cellular processes

08 May 2024 | BioXFEL Publications | Contributor(s): Joseph Yoniles, Jacob A. Summers, Kara Zielinski, Cali Antolini, Mayura Panjalingam, Stella Lisova, Frank R. Moss, Maximus Aldo Di Perna, Christopher Kupitz, Mark S. Hunter, Lois Pollack, Soichi Wakatsuki, Peter D. Dahlberg

https://doi.org/10.1091/mbc.e24-01-0042 Cryogenic electron tomography (cryo-ET) is the highest resolution imaging technique applicable to the life sciences, enabling subnanometer visualization of specimens preserved in their near native states. The rapid plunge freezing process used to prepare …

Abstract 2307 Evaluating the thermal stability of congenital heart diseases-associated TBX5 missense mutants

25 Mar 2024 | BioXFEL Publications | Contributor(s): Alejandro Rivera-Madera, Edwin Peña-Martínez, Jose Arcadio Rodriguez-Martinez

http://dx.doi.org/10.1016/j.jbc.2024.107071 journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Rivera-Madera, A., Peña-Martínez, E., & Rodriguez-Martinez, J. (2024). Abstract 2307 Evaluating the thermal stability of congenital heart diseases-associated TBX5 missense mutants. Journal …

Abstract 1473 Integrating Machine Learning and Functional Genomics to Prioritize CVD-associated Mutations Altering NKX2-5 and TBX5 DNA Binding

25 Mar 2024 | BioXFEL Publications | Contributor(s): Edwin Peña-Martínez, Diego Pomales-Matos, Alejandro Rivera-Madera, Jean Messon-Bird, Joshua Medina-Feliciano, Leandro Sanabria-Alberto, Adriana Barreiro-Rosario, Jeancarlos Rivera-Del Valle, Jose Arcadio Rodriguez-Martinez

http://dx.doi.org/10.1016/j.jbc.2024.106540 journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Peña-Martínez, E., Pomales-Matos, D., Rivera-Madera, A., Messon-Bird, J., Medina-Feliciano, J., Sanabria-Alberto, L., Barreiro-Rosario, A., Rivera-Del Valle, J., & Rodríguez-Martínez, J. …

Decoding Non-coding Variants: Recent Approaches to Studying Their Role in Gene Regulation and Human Diseases

01 Mar 2024 | BioXFEL Publications | Contributor(s): Edwin G. Peña-Martínez, Jose Arcadio Rodriguez-Martinez

http://dx.doi.org/10.31083/j.fbs1601004 journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Peña-Martínez, E. G., & Rodríguez-Martínez, J. A. (2024). Decoding Non-coding Variants: Recent Approaches to Studying Their Role in Gene Regulation and Human Diseases. Frontiers in …

Biochemical and Structural Studies of the Carminomycin 4-O-Methyltransferase DnrK

27 Feb 2024 | BioXFEL Publications | Contributor(s): Elnaz Jalali, Fengbin Wang, Brooke R. Overbay, Mitchell Miller, Khaled A. Shaaban, Larissa V. Ponomareva, Qing Ye, Hoda Saghaeiannejad-Esfahani, Minakshi Bhardwaj, Andrew D. Steele, Christiana N. Teijaro, Ben Shen, Steven G. Van Lanen, Qing-Bai She, S. Randal Voss, George Phillips, Jon S. Thorson

http://dx.doi.org/10.1021/acs.jnatprod.3c00947 journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Jalali, E., Wang, F., Overbay, B. R., Miller, M. D., Shaaban, K. A., Ponomareva, L. V., Ye, Q., Saghaeiannejad-Esfahani, H., Bhardwaj, M., Steele, A. D., Teijaro, C. N., Shen, B., Van …

Conformational dynamics of adenylate kinase in crystals

21 Feb 2024 | BioXFEL Publications | Contributor(s): Junhyung Kim, Sojin Moon, Tod D. Romo, Yifei Yang, Euiyoung Bae, George Phillips

http://dx.doi.org/10.1063/4.0000205 Adenylate kinase is a ubiquitous enzyme in living systems and undergoes dramatic conformational changes during its catalytic cycle. For these reasons, it is widely studied by genetic, biochemical, and biophysical methods, both experimental and theoretical. We …

The Pixel Anomaly Detection Tool: a user-friendly GUI for classifying detector frames using machine-learning approaches

12 Feb 2024 | BioXFEL Publications | Contributor(s): Gihan Kaushylal Ketawala, Caitlin M. Reiter, Petra Fromme, Sabine Botha

http://dx.doi.org/10.1107/s1600576724000116 Data collection at X-ray free electron lasers has particular experimental challenges, such as continuous sample delivery or the use of novel ultrafast high-dynamic-range gain-switching X-ray detectors. This can result in a multitude of data artefacts, …

Sequence-dependent conformational preferences of disordered single-stranded RNA

08 Feb 2024 | BioXFEL Publications | Contributor(s): Tong Wang, Weiwei He, Suzette A. Pabit, Serdal Kirmizialtin, Lois Pollack

http://dx.doi.org/10.1016/j.bpj.2023.11.2762 journal-article Wang, T., He, W., Pabit, S. A., Kirmizialtin, S., & Pollack, L. (2024). Sequence-dependent conformational preferences of disordered single-stranded RNA. Biophysical Journal, 123(3), 453a–454a. …

Role of conformational dynamics in the catalytic mechanism of viral macrodomains

08 Feb 2024 | BioXFEL Publications | Contributor(s): Rishav Mitra, James Fraser

https://doi.org/10.1016/j.bpj.2023.11.2156 journal-article Mitra, R., & Fraser, J. (2024). Role of conformational dynamics in the catalytic mechanism of viral macrodomains. Biophysical Journal, 123(3), 356a–357a. https://doi.org/10.1016/j.bpj.2023.11.2156 Rishav Mitra and James Fraser

Product-stabilized filamentation by human glutamine synthetase allosterically tunes activity

08 Feb 2024 | BioXFEL Publications | Contributor(s): Eric R. Greene, Richard Muniz, Hiroki Yamamura, Samuel Hoff, Angelika Arada, Priyanka Bajaj, Daphne Chen, John D. Lee, Massimiliano Bonomi, Justin M. Kollman, James Fraser

http://dx.doi.org/10.1016/j.bpj.2023.11.2135 journal-article Greene, E. R., Muniz, R., Yamamura, H., Hoff, S., Arada, A., Bajaj, P., Chen, D., Lee, J. D., Bonomi, M., Kollman, J. M., & Fraser, J. (2024). Product-stabilized filamentation by human glutamine synthetase allosterically tunes activity. …

Computing a Bayesian multi-state model of a protein structure from an X-ray diffraction pattern

08 Feb 2024 | BioXFEL Publications | Contributor(s): Matthew P. Hancock, James Fraser, Andrej Sali

http://dx.doi.org/10.1016/j.bpj.2023.11.1276 journal-article Hancock, M. P., Fraser, J. S., & Sali, A. (2024). Computing a Bayesian multi-state model of a protein structure from an X-ray diffraction pattern. Biophysical Journal, 123(3), 200a–201a. https://doi.org/10.1016/j.bpj.2023.11.1276 …

Extracting conformational heterogeneity from 2D and 3D cryo-EM data

08 Feb 2024 | BioXFEL Publications | Contributor(s): Samuel Hoff, Massimiliano Bonomi, James Fraser, Eric Greene

http://dx.doi.org/10.1016/j.bpj.2023.11.376 journal-article Hoff, S., Bonomi, M., Fraser, J., & Greene, E. (2024). Extracting conformational heterogeneity from 2D and 3D cryo-EM data. Biophysical Journal, 123(3), 50a–51a. https://doi.org/10.1016/j.bpj.2023.11.376 Samuel Hoff and Massimiliano …

Blue and red in the protein world: Photoactive yellow protein and phytochromes as revealed by time-resolved crystallography

31 Jan 2024 | BioXFEL Publications | Contributor(s): Marius Schmidt, Emina Stojkovic

http://dx.doi.org/10.1063/4.0000233 Time-resolved crystallography (TRX) is a method designed to investigate functional motions of biological macromolecules on all time scales. Originally a synchrotron-based method, TRX is enabled by the development of TR Laue crystallography (TRLX). TR serial …

Blue and red in the protein world: Photoactive yellow protein and phytochromes as revealed by time-resolved crystallography

31 Jan 2024 | BioXFEL Publications | Contributor(s): Marius Schmidt, Emina Stojkovic

https://doi.org/10.1063/4.0000233 Time-resolved crystallography (TRX) is a method designed to investigate functional motions of biological macromolecules on all time scales. Originally a synchrotron-based method, TRX is enabled by the development of TR Laue crystallography (TRLX). TR serial …

Coronavirus M Protein Trafficking in Epithelial Cells Utilizes a Myosin Vb Splice Variant and Rab10

10 Jan 2024 | BioXFEL Publications | Contributor(s): Lynne A. Lapierre, Joseph T. Roland, Elizabeth H. Manning, Catherine Caldwell, Honor L. Glenn, Pierre-Olivier Vidalain, Frederic Tangy, Brenda Hogue, C. A. M. De Haan, James R. Goldenring

http://dx.doi.org/10.3390/cells13020126 The membrane (M) glycoprotein of coronaviruses (CoVs) serves as the nidus for virion assembly. Using a yeast two-hybrid screen, we identified the interaction of the cytosolic tail of Murine Hepatitis Virus (MHV-CoV) M protein with Myosin Vb (MYO5B), …

Time-resolved Crystallography on Protein Photoreceptors and Enzymes

08 Dec 2023 | BioXFEL Publications | Contributor(s): Marius Schmidt

http://dx.doi.org/10.1039/bk9781837670154-00203 Time-resolved macromolecular crystallography (TRX) unifies structure determination of biomolecules with chemical kinetics. Developed at synchrotron light sources, TRX has been transformed by serial femtosecond crystallography (SFX) at X-ray free …

Prioritizing cardiovascular disease-associated variants altering NKX2-5 and TBX5 binding through an integrative computational approach

03 Nov 2023 | BioXFEL Publications | Contributor(s): Edwin G. Peña-Martínez, Diego A. Pomales-Matos, Alejandro Rivera-Madera, Jean L. Messon-Bird, Joshua G. Medina-Feliciano, Leandro Sanabria-Alberto, Adriana C. Barreiro-Rosario, Jeancarlos Rivera-Del Valle, Jessica M. Rodríguez-Ríos, Jose Arcadio Rodriguez-Martinez

http://dx.doi.org/10.1016/j.jbc.2023.105423 journal-article Peña-Martínez, E. G., Pomales-Matos, D. A., Rivera-Madera, A., Messon-Bird, J. L., Medina-Feliciano, J. G., Sanabria-Alberto, L., Barreiro-Rosario, A. C., Rivera-Del Valle, J., Rodríguez-Ríos, J. M., & Rodríguez-Martínez, J. A. …

Discovery and Clinical Proof-of-Concept of RLY-2608, a First-in-Class Mutant-Selective Allosteric PI3Kα Inhibitor That Decouples Antitumor Activity from Hyperinsulinemia

02 Nov 2023 | BioXFEL Publications | Contributor(s): Andreas Varkaris, Ermira Pazolli, Hakan Gunaydin, Qi Wang, Levi Pierce, Alessandro A. Boezio, Artemisa Bulku, Lucian DiPietro, Cary Fridrich, Adam Frost, Fabrizio Giordanetto, Erika P. Hamilton, Katherine Harris, Michael Holliday, Tamieka L. Hunter, Amanda Iskandar, Yongli Ji, Alexandre Larivée, Jonathan R. LaRochelle, André Lescarbeau, Fabien Llambi, Brenda Lormil, Mary M. Mader, Brenton G. Mar, Iain Martin, Thomas H. McLean, Klaus Michelsen, Yakov Pechersky, Erika Puente-Poushnejad, Kevin Raynor, Dipali Rogala, Ramin Samadani, Alison M. Schram, Kelley Shortsleeves, Sweta Swaminathan, Shahein Tajmir, Gege Tan, Yong Tang, Roberto Valverde, Bryan Wehrenberg, Jeremy Wilbur, Bret R. Williams, Hongtao Zeng, Hanmo Zhang, W. Patrick Walters, Beni B. Wolf, David E. Shaw, Donald A. Bergstrom, James Watters, James Fraser, Pascal D. Fortin, D. Randal Kipp

http://dx.doi.org/10.1158/2159-8290.cd-23-0944 Abstract PIK3CA (PI3Kα) is a lipid kinase commonly mutated in cancer, including ∼40% of hormone receptor–positive breast cancer. The most frequently observed mutants occur in the kinase and …

Identification of the native Torpedo californica nicotinic acetylcholine receptor's glycan composition after a multi‐step sequential purification method using MALDI‐ToF MS

31 Oct 2023 | BioXFEL Publications | Contributor(s): Rafael Maldonado‐Hernández, Orestes Quesada, José A. González‐Feliciano, Abel Baerga‐Ortiz, José A. Lasalde‐Dominicci

http://dx.doi.org/10.1002/pmic.202300151 AbstractThe Cys‐loop pentameric ligand‐gated ion channels comprise a dynamic group of proteins that have been extensively studied for decades, yielding a wealth of findings at both the structural and functional levels. The nicotinic acetylcholine …

Structural analysis of wild-type and Val120Thr mutant Candida boidinii formate dehydrogenase by X-ray crystallography

20 Oct 2023 | BioXFEL Publications | Contributor(s): Mehmet Gul, Busra Yuksel, Huri Bulut, Hasan Demirci

http://dx.doi.org/10.1107/s2059798323008070 Candida boidinii NAD+-dependent formate dehydrogenase (CbFDH) has gained significant attention for its potential application in the production of biofuels and various industrial chemicals from inorganic carbon dioxide. The present study …

Atomistic structure of the SARS-CoV-2 pseudoknot in solution from SAXS-driven molecular dynamics

11 Oct 2023 | BioXFEL Publications | Contributor(s): Weiwei He, Josue San Emeterio, Michael T Woodside, Serdal Kirmizialtin, Lois Pollack

http://dx.doi.org/10.1093/nar/gkad809 Abstract SARS-CoV-2 depends on −1 programmed ribosomal frameshifting (−1 PRF) to express proteins essential for its replication. The RNA pseudoknot stimulating −1 PRF is thus an attractive drug target. However, the structural models of this …

RNA structures and dynamics with Å resolution revealed by x-ray free-electron lasers

27 Sep 2023 | BioXFEL Publications | Contributor(s): Kara Zielinski, Shuo Sui, Suzette A. Pabit, Daniel A. Rivera, Tong Wang, Qingyue Hu, Maithri M. Kashipathy, Stella Lisova, Chris B. Schaffer, Valerio Mariani, Mark S. Hunter, Christopher Kupitz, Frank R. Moss, Frédéric P. Poitevin, Thomas D. Grant, Lois Pollack

http://dx.doi.org/10.1126/sciadv.adj3509 RNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We …

The mythical metal – insights on the accuracy of metal identification in structural biology

26 Sep 2023 | BioXFEL Publications | Contributor(s): Edward Snell, Elspeth F. Garman, Geoff W. Grime, Aina E. Cohen, Sarah EJ Bowman

http://dx.doi.org/10.1107/s2053273323097188 journal-article Snell, E. H., Garman, E. F., Grime, G. W., Cohen, A. E., & Bowman, S. E. J. (2023). The mythical metal – insights on the accuracy of metal identification in structural biology. Acta Crystallographica Section A Foundations and Advances, …

A user-friendly plug-and-play cyclic olefin copolymer-based microfluidic chip for room-temperature, fixed-target serial crystallography

25 Sep 2023 | BioXFEL Publications | Contributor(s): Zhongrui Liu, Kevin Gu, Megan Shelby, Deepshika Gilbile, Artem Y. Lyubimov, Silvia Russi, Aina E. Cohen, Sankar Raju Narayanasamy, Sabine Botha, Christopher Kupitz, Raymond G. Sierra, Fredric Poitevin, Antonio Gilardi, Stella Lisova, Matthew Coleman, Matthias Frank, Tonya L. Kuhl

http://dx.doi.org/10.1107/s2059798323007027 Over the past two decades, serial X-ray crystallography has enabled the structure determination of a wide range of proteins. With the advent of X-ray free-electron lasers (XFELs), ever-smaller crystals have yielded high-resolution diffraction and …

Mapping protein dynamics at high spatial resolution with temperature-jump X-ray crystallography

18 Sep 2023 | BioXFEL Publications | Contributor(s): Alexander M. Wolff, Eriko Nango, Iris Diane Young, Aaron S. Brewster, Minoru Kubo, Takashi Nomura, Michihiro Sugahara, Shigeki Owada, Benjamin A. Barad, Kazutaka Ito, Asmit Bhowmick, Sergio Carbajo, Tomoya Hino, James Holton, Dohyun Im, Lee J. O’Riordan, Tomoyuki Tanaka, Rie Tanaka, Raymond G. Sierra, Fumiaki Yumoto, Kensuke Tono, So Iwata, Nicholas K. Sauter, James Fraser, Michael Thompson

http://dx.doi.org/10.1038/s41557-023-01329-4 AbstractUnderstanding and controlling protein motion at atomic resolution is a hallmark challenge for structural biologists and protein engineers because conformational dynamics are essential for complex functions such as enzyme catalysis and allosteric …

Synthesis of Novel Heterocyclic Ferrocenyl Chalcones and Their Biological Evaluation

11 Sep 2023 | BioXFEL Publications | Contributor(s): Ámbar M. Alsina-Sánchez, Sebastián Montalvo-Vázquez, Nilmary Grafals-Ruiz, Carmen Acosta, Emily M. Ormé, Israel Rodriguez, Sara M. Delgado-Rivera, Arthur Tinoco, Suranganie Dharmawardhane, Ingrid C. Montes-González

http://dx.doi.org/10.1021/acsomega.3c01830 journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Alsina-Sánchez, Á. M., Montalvo-Vázquez, S., Grafals-Ruiz, N., Acosta, C., Ormé, E. M., Rodríguez, I., Delgado-Rivera, S. M., Tinoco, A. D., Dharmawardhane, S., & Montes-González, I. C. …

Detection of a Geminate Photoproduct of Bovine Cytochrome c Oxidase by Time-Resolved Serial Femtosecond Crystallography

11 Sep 2023 | BioXFEL Publications | Contributor(s): Izumi Ishigami, Sergio Carbajo, Nadia Zatsepin, Masahide Hikita, Chelsie E Conrad, Garrett Charles Nelson, Jesse David Coe, Shibom Basu, Thomas Grant, Matthew H. Seaberg, Raymond G. Sierra, Mark S. Hunter, Petra Fromme, Raimund Fromme, Denis L. Rousseau, Syun-Ru Yeh

http://dx.doi.org/10.1021/jacs.3c07803 journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Ishigami, I., Carbajo, S., Zatsepin, N., Hikita, M., Conrad, C. E., Nelson, G., Coe, J., Basu, S., Grant, T., Seaberg, M. H., Sierra, R. G., Hunter, M. S., Fromme, P., Fromme, R., Rousseau, D. …

A type 2 immune circuit in the stomach controls mammalian adaptation to dietary chitin

07 Sep 2023 | BioXFEL Publications | Contributor(s): Do-Hyun Kim, Yilin Wang, Haerin Jung, Rachael L. Field, Xinya Zhang, Ta-Chiang Liu, Changqing Ma, James Fraser, Jonathan R. Brestoff, Steven J. Van Dyken

http://dx.doi.org/10.1126/science.add5649 Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic …

Heterogeneity in M. tuberculosis β-lactamase inhibition by Sulbactam

07 Sep 2023 | BioXFEL Publications | Contributor(s): Tek Narsingh Malla, Kara Zielinski, Luis Aldama, Sasa Bajt, Denisse Feliz, Brendon Hayes, Mark S. Hunter, Christopher Kupitz, Stella Lisova, Juraj Knoska, Jose Manuel Martin-Garcia, Valerio Mariani, Suraj Pandey, Ishwor Poudyal, Raymond G. Sierra, Alexandra Tolstikova, Oleksandr Yefanov, Chung Hong Yoon, Abbas Ourmazd, Petra Fromme, Peter Schwander, Anton Barty, Henry Chapman, Emina Stojkovic, Alexander Batyuk, Sébastien Boutet, George Phillips, Lois Pollack, Marius Schmidt

http://dx.doi.org/10.1038/s41467-023-41246-1 AbstractFor decades, researchers have elucidated essential enzymatic functions on the atomic length scale by tracing atomic positions in real-time. Our work builds on possibilities unleashed by mix-and-inject serial crystallography (MISC) at X-ray free …

A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo

31 Aug 2023 | BioXFEL Publications | Contributor(s): Taha Y. Taha, Rahul K. Suryawanshi, Irene P. Chen, Galen J. Correy, Maria McCavitt-Malvido, Patrick C. O’Leary, Manasi P. Jogalekar, Morgan E. Diolaiti, Gabriella R. Kimmerly, Chia-Lin Tsou, Ronnie Gascon, Mauricio Montano, Luis Martinez-Sobrido, Nevan J. Krogan, Alan Ashworth, James Fraser, Melanie Ott

http://dx.doi.org/10.1371/journal.ppat.1011614 Despite unprecedented efforts, our therapeutic arsenal against SARS-CoV-2 remains limited. The conserved macrodomain 1 (Mac1) in NSP3 is an enzyme exhibiting ADP-ribosylhydrolase activity and a possible drug target. To determine the role of Mac1 …

Numerical modeling reveals improved organelle separation for dielectrophoretic ratchet migration

25 Aug 2023 | BioXFEL Publications | Contributor(s): Domin Koh, Mukul Sonker, Edgar A. Arriaga, Alexandra Ros

http://dx.doi.org/10.1002/elps.202300091 AbstractOrganelle size varies with normal and abnormal cell function. Thus, size‐based particle separation techniques are key to assessing the properties of organelle subpopulations differing in size. Recently, insulator‐based dielectrophoresis (iDEP) …

Practical considerations for the analysis of time-resolved x-ray data

16 Aug 2023 | BioXFEL Publications | Contributor(s): Marius Schmidt

http://dx.doi.org/10.1063/4.0000196 The field of time-resolved macromolecular crystallography has been expanding rapidly after free electron lasers for hard x rays (XFELs) became available. Techniques to collect and process data from XFELs spread to synchrotron light sources. Although time-scales …

Viral anti‐inflammatory serpin reduces immuno‐coagulopathic pathology in SARS‐CoV‐2 mouse models of infection

03 Aug 2023 | BioXFEL Publications | Contributor(s): Liqiang Zhang, Yize (Henry) Li, Karen Kibler, Simona Kraberger, Arvind Varsani, Julie Turk, Nora Elmadbouly, Emily Aliskevich, Laurel Spaccarelli, Bereket Estifanos, Junior Enow, Isabela Rivabem Zanetti, Nicholas Saldevar, Efrem Lim, Jessika Schlievert, Kyle Browder, Anjali Wilson, Fernando Arcos Juan, Aubrey Pinteric, Aman Garg, Henna Monder, Rohan Saju, Savanah Gisriel, Bertram Jacobs, Timothy L Karr, Esther Borges Florsheim, Vivek Kumar, John Wallen, Masmudur Rahman, Grant McFadden, Brenda Hogue, Alexandra R Lucas

http://dx.doi.org/10.15252/emmm.202317376 AbstractSARS‐CoV‐2 acute respiratory distress syndrome (ARDS) induces uncontrolled lung inflammation and coagulopathy with high mortality. Anti‐viral drugs and monoclonal antibodies reduce early COVID‐19 severity, but treatments for late‐stage …

Crystal Structure of 4-Hydroxybutyryl-CoA Synthetase (ADP-forming): A Key Enzyme in the Thaumarchaeal Hydroxypropionate/Hydroxybutyrate cycle

31 Jul 2023 | BioXFEL Publications | Contributor(s): Hasan Demirci, J Johnson, Bradley Tolar, Bilge Tosun, Yasuo Yoshikuni, Christopher Francis, Soichi Wakatsuki

http://dx.doi.org/10.21203/rs.3.rs-3173078/v1 Abstract The 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle from ammonia-oxidizing Thaumarchaeota is currently considered the most energy-efficient aerobic carbon fixation pathway. The Nitrosopumilus maritimus 4-hydroxybutyryl-CoA …

Refinement of multiconformer ensemble models from multi-temperature X-ray diffraction data

27 Jul 2023 | BioXFEL Publications | Contributor(s): Siyuan Du, Stephanie A. Wankowicz, Filip Yabukarski, Tzanko Doukov, Daniel Herschlag, James Fraser

http://dx.doi.org/10.1016/bs.mie.2023.06.009 book-chapter Du, S., Wankowicz, S. A., Yabukarski, F., Doukov, T., Herschlag, D., & Fraser, J. S. (2023). Refinement of multiconformer ensemble models from multi-temperature X-ray diffraction data. Methods in Enzymology. …

A deep learning solution for crystallographic structure determination

25 May 2023 | BioXFEL Publications | Contributor(s): Tom Pan, Shikai Jin, Mitchell Miller, Anastasios Kyrillidis, George Phillips

http://dx.doi.org/10.1107/s2052252523004293 The general de novo solution of the crystallographic phase problem is difficult and only possible under certain conditions. This paper develops an initial pathway to a deep learning neural network approach for the phase problem in protein crystallography, …

Rapid and efficient ambient temperature X-ray crystal structure determination at Turkish Light Source

19 May 2023 | BioXFEL Publications | Contributor(s): Mehmet Gul, Esra Ayan, Ebru Destan, J. Austin Johnson, Alaleh Shafiei, Abdullah Kepceoğlu, Merve Yilmaz, Fatma Betül Ertem, İlkin Yapici, Bilge Tosun, Nilüfer Baldir, Nurettin Tokay, Zeliş Nergiz, Gözde Karakadioğlu, Seyide Seda Paydos, Cahine Kulakman, Cengiz Kaan Ferah, Ömür Güven, Necati Atalay, Enver Kamil Akcan, Haluk Cetinok, Nazlı Eylül Arslan, Kardelen Şabanoğlu, Bengisu Aşci, Serra Tavli, Helin Gümüsboğa, Sevde Altuntaş, Masami Otsuka, Mikako Fujita, Şaban Teki̇n, Halilibrahim Çi̇ftçi̇, Serdar Durdaği, Ezgi Karaca, Burcu Kaplan Türköz, Burak Veli Kabasakal, Ahmet Kati, Hasan DeMi̇rci̇

http://dx.doi.org/10.1038/s41598-023-33989-0 AbstractHigh-resolution biomacromolecular structure determination is essential to better understand protein function and dynamics. Serial crystallography is an emerging structural biology technique which has fundamental limitations due to either sample …

Chaotic advection mixer for capturing transient states of diverse biological macromolecular systems with time-resolved small-angle X-ray scattering

02 May 2023 | BioXFEL Publications | Contributor(s): Kara Zielinski, Andrea Katz, George Douglas Calvey, Suzette A. Pabit, Shawn K. Milano, Cody Aplin, Josue San Emeterio, Richard A. Cerione, Lois Pollack

http://dx.doi.org/10.1107/s2052252523003482 Advances in time-resolved structural techniques, mainly in macromolecular crystallography and small-angle X-ray scattering (SAXS), allow for a detailed view of the dynamics of biological macromolecules and reactions between binding partners. Of particular …

Copper Based Antibacterial Compounds: Potential Targeting Pathways and Current Drug Design Trends.

28 Apr 2023 | BioXFEL Publications | Contributor(s): Aixa M. Orta-Rivera, Yazmary Meléndez-Contés, Nataniel Rivera-Berríos, Adriana M. Gómez-Cardona, Andrés Ramos-Rodríguez, Claudia Cruz-Santiago, Christian González-Dumeng, Janangelis López, Jansteven Escribano, Jared J. Rivera-Otero, Josean Díaz-Rivera, Sebastián C. Díaz-Vélez, Zulemaría Feliciano-Delgado, Arthur Tinoco

http://dx.doi.org/10.20944/preprints202304.1124.v1 Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next generation …

Inter-Bragg crystallographic phase retrieval from shape transforms, stacking faults and substitutional disorder

31 Mar 2023 | BioXFEL Publications | Contributor(s): J.P.J. Chen, K. Pande, J.J. Donatelli, A.V. Martin, K. Ayyer, H.N. Chapman, R. Bean, K.E. Schmidt, R.A. Kirian

http://dx.doi.org/10.1016/j.ultramic.2023.113728 journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Chen, J. P. J., Pande, K., Donatelli, J. J., Martin, A. V., Ayyer, K., Chapman, H. N., Bean, R., Schmidt, K. E., & Kirian, R. A. (2023). Inter-Bragg crystallographic phase retrieval …

Randomness in time-resolved serial crystallography data: alternatives to the binning and averaging approach

17 Mar 2023 | BioXFEL Publications | Contributor(s): C. Casadei, A. Hosseinizadeh, G. Schertler, A. Ourmazd, R. Santra

http://dx.doi.org/10.1107/s2053273322095742 journal-article Casadei, C., Hosseinizadeh, A., Schertler, G., Ourmazd, A., & Santra, R. (2022). Randomness in time-resolved serial crystallography data: alternatives to the binning and averaging approach. Acta Crystallographica Section A Foundations …

Polymer-based microfluidic device for on-chip counter-diffusive crystallization and in situ X-ray crystallography at room temperature

13 Mar 2023 | BioXFEL Publications | Contributor(s): Sarthak Saha, Can Özden, Alfred Samkutty, Silvia Russi, Aina Cohen, Margaret M. Stratton, Sarah Perry

http://dx.doi.org/10.1039/d2lc01194h Here we have reported novel polymeric devices to control fluid flow using surface forces and capillary action to facilitate counter-diffusive, on-chip protein crystallization. journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Saha, S., Özden, C., …

Robust total X-ray scattering workflow to study correlated motion of proteins in crystals

03 Mar 2023 | BioXFEL Publications | Contributor(s): Steve P. Meisburger, David Case, Nozomi Ando

http://dx.doi.org/10.1038/s41467-023-36734-3 AbstractThe breathing motions of proteins are thought to play a critical role in function. However, current techniques to study key collective motions are limited to spectroscopy and computation. We present a high-resolution experimental approach based …

20 years of crystal hits: progress and promise in ultrahigh-throughput crystallization screening

27 Feb 2023 | BioXFEL Publications | Contributor(s): Miranda Lynch, M. Elizabeth Snell, Stephen A. Potter, Edward Snell, Sarah EJ Bowman

http://dx.doi.org/10.1107/s2059798323001274 Diffraction-based structural methods contribute a large fraction of the biomolecular structural models available, providing a critical understanding of macromolecular architecture. These methods require crystallization of the target molecule, which …

DIMPLE: deep insertion, deletion, and missense mutation libraries for exploring protein variation in evolution, disease, and biology

24 Feb 2023 | BioXFEL Publications | Contributor(s): Christian B. Macdonald, David Nedrud, Patrick Rockefeller Grimes, Donovan Trinidad, James Fraser, Willow Coyote-Maestas

http://dx.doi.org/10.1186/s13059-023-02880-6 AbstractInsertions and deletions (indels) enable evolution and cause disease. Due to technical challenges, indels are left out of most mutational scans, limiting our understanding of them in disease, biology, and evolution. We develop a low cost and bias …

Biological function investigated by time-resolved structure determination

21 Feb 2023 | BioXFEL Publications | Contributor(s): Marius Schmidt

http://dx.doi.org/10.1063/4.0000177 Inspired by recent progress in time-resolved x-ray crystallography and the adoption of time-resolution by cryo-electronmicroscopy, this article enumerates several approaches developed to become bigger/smaller, faster, and better to gain new insight into the …

Data assimilation in operator algebras

17 Feb 2023 | BioXFEL Publications | Contributor(s): David Freeman, Dimitrios Giannakis, Brian Mintz, Abbas Ourmazd, Joanna Slawinska

http://dx.doi.org/10.1073/pnas.2211115120 We develop an algebraic framework for sequential data assimilation of partially observed dynamical systems. In this framework, Bayesian data assimilation is embedded in a nonabelian operator algebra, which provides a representation of observables by …

Reaction coordinate dependent fibrillar formation of human glutamine synthetase tunes activity

10 Feb 2023 | BioXFEL Publications | Contributor(s): Eric R. Greene, Richard Muniz, Angelika Arada, D. John Lee, Daphne Chen, Erin Thompson, Hiroki Yamamura, Justin M. Kollman, James Fraser

http://dx.doi.org/10.1016/j.bpj.2022.11.2541 journal-article Greene, E. R., Muniz, R., Arada, A., Lee, D. J., Chen, D., Thompson, E., Yamamura, H., Kollman, J. M., & Fraser, J. (2023). Reaction coordinate dependent fibrillar formation of human glutamine synthetase tunes activity. Biophysical …

X-ray scattering exhibits time-resolved view of rhodopsin activation

10 Feb 2023 | BioXFEL Publications | Contributor(s): C. Swathi K. Menon, Konstantinos Karpos, Thomas D. Grant, Andrey V. Struts, Steven D.E. Fried, Suchithranga M.D.C. Perera, Irina V. Kosheleva, Leslie Salas-Estrada, Alan Grossfield, Petra Fromme, Richard Kirian, Michael F. Brown

http://dx.doi.org/10.1016/j.bpj.2022.11.1170 journal-article Menon, C. S. K., Karpos, K., Grant, T. D., Struts, A. V., Fried, S. D. E., Perera, S. M. D. C., Kosheleva, I. V., Salas-Estrada, L., Grossfield, A., Fromme, P., Kirian, R. A., & Brown, M. F. (2023). X-ray scattering exhibits …

Large language models generate functional protein sequences across diverse families

26 Jan 2023 | BioXFEL Publications | Contributor(s): Ali Madani, Ben Krause, Eric R. Greene, Subu Subramanian, Benjamin P. Mohr, James Holton, Jose Luis Olmos, Caiming Xiong, Zachary Z. Sun, Richard Socher, James Fraser, Nikhil Naik

http://dx.doi.org/10.1038/s41587-022-01618-2 journal-article Madani, A., Krause, B., Greene, E. R., Subramanian, S., Mohr, B. P., Holton, J. M., Olmos, J. L., Xiong, C., Sun, Z. Z., Socher, R., Fraser, J. S., & Naik, N. (2023). Large language models generate functional protein sequences across …

Energy landscapes from cryo-EM snapshots: a benchmarking study

25 Jan 2023 | BioXFEL Publications | Contributor(s): Raison Dsouza, Ghoncheh Mashayekhi, Roshanak Etemadpour, Peter Schwander, Abbas Ourmazd

http://dx.doi.org/10.1038/s41598-023-28401-w AbstractBiomolecules undergo continuous conformational motions, a subset of which are functionally relevant. Understanding, and ultimately controlling biomolecular function are predicated on the ability to map continuous conformational motions, and …

Poster Template PPT

19 Jan 2023 | Downloads | Contributor(s): Nicole Terranova

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Room-temperature structural studies of SARS-CoV-2 protein NendoU with an X-ray free-electron laser

10 Jan 2023 | BioXFEL Publications | Contributor(s): Rebecca Jeanne Jernigan, Dhenugen Logeswaran, Diandra Doppler, Nirupa Nagaratnam, Mukul Sonker, Jay-How Yang, Gihan Kaushylal Ketawala, Jose M. Martin-Garcia, Megan Shelby, Thomas D. Grant, Valerio Mariani, Alexandra Tolstikova, Michelle Z. Sheikh, Mimi Cho Yung, Matthew Coleman, Sahba Zaare, Emily K. Kaschner, Mohammad Towshif Rabbani, Reza Nazari, Michele A. Zacks, Brandon Hayes, Raymond G. Sierra, Mark S. Hunter, Stella Lisova, Alexander Batyuk, Christopher Kupitz, Sebastien Boutet, Debra T. Hansen, Richard Kirian, Marius Schmidt, Raimund Fromme, Matthias Frank, Alexandra Ros, Julian J.-L. Chen, Sabine Botha, Petra Fromme

http://dx.doi.org/10.1016/j.str.2022.12.009 journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Jernigan, R. J., Logeswaran, D., Doppler, D., Nagaratnam, N., Sonker, M., Yang, J.-H., Ketawala, G., Martin-Garcia, J. M., Shelby, M. L., Grant, T. D., Mariani, V., Tolstikova, A., Sheikh, …

Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2

04 Jan 2023 | BioXFEL Publications | Contributor(s): Stefan Gahbauer, Galen J. Correy, Marion Schuller, Matteo P. Ferla, Yagmur Umay Doruk, Moira Rachman, Taiasean Wu, Morgan Diolaiti, Siyi Wang, R. Jeffrey Neitz, Daren Fearon, Dmytro S. Radchenko, Yurii S. Moroz, John J. Irwin, Adam R. Renslo, Jenny C. Taylor, Jason E. Gestwicki, Frank Von Delft, Alan Ashworth, Ivan Ahel, Brian K. Shoichet, James Fraser

http://dx.doi.org/10.1073/pnas.2212931120 The nonstructural protein 3 (NSP3) of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) contains a conserved macrodomain enzyme (Mac1) that is critical for pathogenesis and lethality. While small-molecule inhibitors of Mac1 have great …

The crystal structure of Vibrio cholerae (6-4) photolyase reveals interactions with cofactors and a DNA-binding region

14 Dec 2022 | BioXFEL Publications | Contributor(s): Baris Cakilkaya, Ibrahim Halil Kavakli, Hasan Demirci

http://dx.doi.org/10.1016/j.jbc.2022.102794 journal-article Cakilkaya, B., Kavakli, I. H., & DeMirci, H. (2023). The crystal structure of Vibrio cholerae (6-4) photolyase reveals interactions with cofactors and a DNA-binding region. Journal of Biological Chemistry, 299(1), 102794. …

Regulation of light energy conversion between linear and cyclic electron flow within photosystem II controlled by the plastoquinone/quinol redox poise

27 Nov 2022 | BioXFEL Publications | Contributor(s): Colin Gates, Gennady Ananyev, Shatabdi Roy-Chowdhury, Petra Fromme, G. Charles Dismukes

http://dx.doi.org/10.1007/s11120-022-00985-w journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Gates, C., Ananyev, G., Roy-Chowdhury, S., Fromme, P., & Dismukes, G. C. (2022). Regulation of light energy conversion between linear and cyclic electron flow within photosystem II …

Protein motions visualized by femtosecond time-resolved crystallography: The case of photosensory vs photosynthetic proteins

14 Oct 2022 | BioXFEL Publications | Contributor(s): Sebastian Westenhoff, Petra Meszaros, Marius Schmidt

http://dx.doi.org/10.1016/j.sbi.2022.102481 journal-article Westenhoff, S., Meszaros, P., & Schmidt, M. (2022). Protein motions visualized by femtosecond time-resolved crystallography: The case of photosensory vs photosynthetic proteins. Current Opinion in Structural Biology, 77, 102481. …

Identification of New L-Heptanoylphosphatidyl Inositol Pentakisphosphate Derivatives Targeting the Interaction with HIV-1 Gag by Molecular Modelling Studies

12 Oct 2022 | BioXFEL Publications | Contributor(s): Halilibrahim Ciftci, Belgin Sever, Esra Ayan, Mustafa Can, Hasan Demirci, Masami Otsuka, Amaç Fatih TuYuN, Hiroshi Tateishi, Mikako Fujita

http://dx.doi.org/10.3390/ph15101255 The HIV-1 Gag protein binds to the host cell membrane and assembles into immature particles. Then, in the course of immature virion budding, activated protease cleaves Gag into its main components: MA, CA, NC, and p6 proteins. The highly basic residues of MA …

A language model beats alphafold2 on orphans

03 Oct 2022 | BioXFEL Publications | Contributor(s): Jennifer M. Michaud, Ali Madani, James Fraser

http://dx.doi.org/10.1038/s41587-022-01466-0 journal-article Michaud, J. M., Madani, A., & Fraser, J. S. (2022). A language model beats alphafold2 on orphans. Nature Biotechnology, 40(11), 1576–1577. https://doi.org/10.1038/s41587-022-01466-0 Jennifer M. Michaud and Ali Madani and James S. …

Electrically stimulated droplet injector for reduced sample consumption in serial crystallography

29 Sep 2022 | BioXFEL Publications | Contributor(s): Mukul Sonker, Diandra Doppler, Ana Egatz-Gomez, Sahba Zaare, Mohammad T. Rabbani, Abhik Manna, Jorvani Cruz Villarreal, Garrett Charles Nelson, Gihan Kaushylal Ketawala, Konstantinos Karpos, Roberto C. Alvarez, Reza Nazari, Darren Gary Thifault, Rebecca Jeanne Jernigan, Dominik Oberthür, Huijong Han, Raymond Sierra, Mark S. Hunter, Alexander Batyuk, Christopher Kupitz, Robert E. Sublett, Frederic Poitevin, Stella Lisova, Valerio Mariani, Alexandra Tolstikova, Sebastien Boutet, Marc Messerschmidt, J. Domingo Meza-Aguilar, Raimund Fromme, Jose M. Martin-Garcia, Sabine Botha, Petra Fromme, Thomas D. Grant, Richard Kirian, Alexandra Ros

http://dx.doi.org/10.1016/j.bpr.2022.100081 journal-article NSF-STC Biology with X-ray Lasers (NSF-1231306) Sonker, M., Doppler, D., Egatz-Gomez, A., Zaare, S., Rabbani, M. T., Manna, A., Cruz Villarreal, J., Nelson, G., Ketawala, G. K., Karpos, K., Alvarez, R. C., Nazari, R., Thifault, D., …