Article
Chemistry, Physical
Dong Zhang, Jun Li, Shi-Jie Chen
Summary: This study introduces a coarse-grained RNA model named IsRNA1, which can predict native structures of small RNAs and fold medium-sized RNAs into near-native structures through molecular dynamics simulations. IsRNA1 exhibits improved performance in predicting structures of relatively large RNAs with complex topologies in a large-scale benchmark test for RNA 3D structure prediction.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Multidisciplinary
Jihyun Kim, Mihajlo Novakovic, Sundaresan Jayanthi, Adonis Lupulescu, Eriks Kupce, J. Tassilo Grun, Klara Mertinkus, Andreas Oxenfarth, Christian Richter, Robbin Schnieders, Julia Wirmer-Bartoschek, Harald Schwalbe, Lucio Frydman
Summary: This study introduces a heteronuclear-resolved version of NOESY experiments, which controls magnetization transfers by selecting specific chemical shift combinations to enhance cross-peaks, greatly facilitating RNA assignments and secondary structure determinations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Annalisa D'Arco, Marta Di Fabrizio, Tiziana Mancini, Rosanna Mosetti, Salvatore Macis, Giovanna Tranfo, Giancarlo Della Ventura, Augusto Marcelli, Massimo Petrarca, Stefano Lupi
Summary: In this study, the conformation of the S1 subunits of MERS-CoV, SARS-CoV, and SARS-CoV-2 were investigated by measuring their Amide I infrared absorption bands. The results showed significant differences in the S1 secondary structure of SARS-CoV-2 compared to MERS-CoV and SARS-CoV, including a significant presence of extended beta-sheets. Additionally, the SARS-CoV-2 S1 conformation exhibited significant changes in mild acidic and alkaline pH conditions compared to serological pH. These findings suggest the potential of infrared spectroscopy in studying the secondary structure adaptation of SARS-CoV-2 S1 in different environments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Takuo Osawa, Mari Aoki, Haruhiko Ehara, Shun-ichi Sekine
Summary: Dengue is a mosquito-borne viral infection caused by dengue virus (DENV). The cryoelectron microscopy (cryo-EM) structures of DENV genome replication process have been revealed, which include SLA-bound NS5, NS3-bound PC, and an RNA-elongating NS5-NS3 complex. These structures shed light on the key steps of DENV genome replication, providing foundations for combating flaviviruses.
Review
Biotechnology & Applied Microbiology
Carlos F. S. Costa, Armenio J. M. Barbosa, Ana Margarida G. C. Dias, Ana Cecilia A. Roque
Summary: This article summarizes natural, engineered, and designed affinity ligands targeting the spike protein of SARS-CoV-2, emphasizing key points in molecular recognition, and highlighting the importance of lessons learned from the Covid-19 pandemic in protein engineering.
BIOTECHNOLOGY ADVANCES
(2022)
Editorial Material
Chemistry, Multidisciplinary
Lijun Quan, Tingfang Wu, Qiang Lyu
Summary: This article discusses the importance of proteins as the foundation of life, specifically focusing on the significance of secondary structures for protein functioning. Buehler and his team introduce deep learning models to generate novel proteins with specific secondary structure constraints, likening it to constructing a functional house based on desired keystones.
Article
Chemistry, Multidisciplinary
Sebastian Pomplun, Muhammad Jbara, Anthony J. Quartararo, Genwei Zhang, Joseph S. Brown, Yen-Chun Lee, Xiyun Ye, Stephanie Hanna, Bradley L. Pentelute
Summary: The research team used affinity selection-mass spectrometry to rapidly discover synthetic high-affinity peptide binders for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. These findings serve as a starting point for the development of SARS-CoV-2 diagnostics or conjugates for virus-directed delivery of therapeutics.
ACS CENTRAL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Natacha S. Ogando, Priscila El Kazzi, Jessika C. Zevenhoven-Dobbe, Brenda W. Bontes, Alice Decombe, Clara C. Posthuma, Volker Thiel, Bruno Canard, Francois Ferron, Etienne Decroly, Eric J. Snijder
Summary: The study found that N7-MTase is a critical enzyme for betacoronavirus replication and essential for virus viability. By conducting mutagenesis experiments on betacoronavirus nonstructural protein 14, key residues of the catalytic pocket were identified, which could be targeted for designing inhibitors with potential pan-coronaviral activity spectrum.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Asgar H. Ansari, Manoj Kumar, Sajal Sarkar, Souvik Maiti, Debojyoti Chakraborty, Tony Yuen
Summary: CRISPR-based diagnostics (CRISPRDx) have improved clinical decision-making during the COVID-19 pandemic. A web server called CriSNPr is introduced for designing guide RNAs (gRNAs) and validating oligonucleotide sequences for CRISPRDx. CriSNPr also provides a database of pre-designed gRNAs and target/off-target information for human and SARS-CoV-2 variants. The versatility and applicability of CriSNPr have been validated on multiple Cas proteins.
Article
Biochemical Research Methods
Michelle V. Gadush, Giuseppe A. Sautto, Hamssika Chandrasekaran, Alena Bensussan, Ted M. Ross, Gregory C. Ippolito, Maria D. Person
Summary: In this study, a mass spectrometric method was developed to determine the complete protein sequence of monoclonal antibodies. The method was refined on known sequences and successfully determined high confidence sequences for unknown antibodies. This method has significant practical implications for studying antibody sequences.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Multidisciplinary Sciences
Nicolo Gozzi, Michele Tizzoni, Matteo Chinazzi, Leo Ferres, Alessandro Vespignani, Nicola Perra
Summary: This study explored the spatiotemporal spread of SARS-CoV-2 in Santiago de Chile using anonymized mobile phone data, finding that more developed and wealthier areas experienced a lower burden of the pandemic after government interventions. The impact of NPIs on individuals' mobility was found to correlate with the Human Development Index of comunas in the city.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Xiao Luo, Xiongbin Kang, Alexander Schoenhuth
Summary: Researchers have introduced a novel approach called Strainline that allows for the assembly of viral haplotypes from noisy long reads without a reference genome. Benchmarking on simulated and real datasets of varying complexity and diversity confirms the novelty and superiority of Strainline.
Article
Gastroenterology & Hepatology
Nicholas A. Preziosi, Areeba H. Rizvi, John D. Feerick, Chetan Mandelia
Summary: This report presents two sisters who developed acute onset hematochezia concurrently with SARS-CoV-2 infection. One patient recovered completely, whereas the other sibling developed chronic symptoms leading to a diagnosis of ulcerative colitis requiring biologic therapy.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Aaron Morris, William McCorkindale, Nir Drayman, John D. Chodera, Savas Tay, Nir London, Alpha A. Lee
Summary: The research team used machine learning for novel compound design and synthesis route prediction, successfully identifying chemical scaffolds with antiviral activity. These findings are significant for the development of patent-free antiviral drugs.
CHEMICAL COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Ronny Lorenz, Peter F. Stadler
Summary: The accuracy of RNA secondary structure prediction is affected by the span of base pairs, and algorithms can be specialized to optimize memory usage, but this may sacrifice finding the globally optimal structure. An efficient backtracking algorithm has been integrated into the ViennaRNA package for reconstructing the globally optimal structure, while constraining the z-scores can help identify hyper-stable structural elements in genomic sequences.
Article
Multidisciplinary Sciences
Johan O. L. Andreassona, Michael R. Gotrikb, Michelle J. Wuc, Hannah K. Wayment-Steeled, Wipapat Kladwang, Fernando Portela, Roger Wellington-Oguri, Eterna Participants, Rhiju Das, William J. Greenleafa
Summary: This research presents high-throughput methods for molecular characterization of nucleic acids, enabling crowdsourcing of RNA sensor design and functional testing. Iterative design testing of thousands of crowdsourced RNA sensor designs resulted in near-thermodynamically optimal and reversible RNA switches that couple small molecule inputs to protein binding and fluorogenic outputs. This work proposes a paradigm for widely distributed experimental bioscience.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Shanshan Li, Michael Z. Palo, Grigore Pintilie, Xiaojing Zhang, Zhaoming Su, Kalli Kappel, Wah Chiu, Kaiming Zhang, Rhiju Das
Summary: The Tetrahymena group I intron has provided valuable insights into the folding and misfolding of RNA. In this study, cryo-EM was used to visualize the misfolded structures of the Tetrahymena L-21 ScaI ribozyme. Multiple misfolded substates were identified and compared to the native state, revealing topological differences that explain the failure of substrate docking and suggest pathways for refolding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biotechnology & Applied Microbiology
Syed Usman Enam, Joshua L. Cherry, Susan R. Leonard, Ivan N. Zheludev, David J. Lipman, Andrew Z. Fire
Summary: A nuclease-based approach is developed to enrich DNA from specific organisms, improving the sensitivity of metagenomic sequencing. This method allows for rapid enrichment of pathogenic bacteria and can also be used to enrich for modified DNA that may go unnoticed in metagenomic samples.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Camila Kofman, Andrew M. Watkins, Do Soon Kim, Jessica A. Willi, Alexandra C. Wooldredge, Ashty S. Karim, Rhiju Das, Michael C. Jewett
Summary: Understanding how modifications to the ribosome affect its function is important for various applications, such as studying ribosome biogenesis and repurposing ribosomes for synthetic biology. However, designing sequence-modified ribosomes has been challenging due to functional limitations caused by point mutations, especially in the catalytic active site. In this study, a computational rRNA design approach was developed to overcome these limitations and successfully engineer ribosomes with mutant active sites. The approach also identified new epistatic interactions and improved ribosomal phenotypes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Andriy Kryshtafovych, Maciej Antczak, Marta Szachniuk, Tomasz Zok, Rachael C. Kretsch, Ramya Rangan, Phillip Pham, Rhiju Das, Xavier Robin, Gabriel Studer, Janani Durairaj, Jerome Eberhardt, Aaron Sweeney, Maya Topf, Torsten Schwede, Krzysztof Fidelis, John Moult
Summary: Prediction categories in CASP experiments are updated according to specific issues in structure modeling. CASP15 introduced four new categories: RNA structure, ligand-protein complexes, accuracy of oligomeric structures and their interfaces, and ensembles of alternative conformations. This paper provides technical specifications for these categories and explains their integration in the CASP data management system.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Multidisciplinary Sciences
Marco Forgia, Beatriz Navarro, Stefania Daghino, Amelia Cervera, Andreas Gisel, Silvia Perotto, Dilzara N. Aghayeva, Mary F. Akinyuwa, Emanuela Gobbi, Ivan N. Zheludev, Robert C. Edgar, Rayan Chikhi, Massimo Turina, Artem Babaian, Francesco Di Serio, Marcos de la Pena
Summary: RNA viruses are remnants of the pre-cellular RNA world, and viroid-like elements are small, circular RNA genomes that encode self-cleaving catalytic RNAs. This study identifies a higher number of candidate viroid-like elements than previously thought and reveals that fungal ambiviruses display hybrid features of viroid-like RNAs and viruses. The discovery of similar circular RNAs in fungal viruses further highlights fungi as an evolutionary hub for RNA viruses and viroid-like elements.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Antje M. Krueger, Andrew Watkins, Roger Wellington-Oguri, Jonathan Romano, Camila Kofman, Alysse DeFoe, Yejun Kim, Jeff Anderson-Lee, Eli Fisker, Jill E. Townley, Anne d'Aquino, Rhiju C. Das, Michael Jewett
Summary: By integrating community science and experimental screening, the authors have developed a method for rational design of ribosomes with beneficial properties. They use an online video game, Eterna, to crowdsource RNA sequence design and apply their framework to discover mutant rRNA sequences that improve protein synthesis and cell growth. This work provides insights into rRNA sequence-function relationships and has implications for synthetic biology.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Rhiju Das, Rachael C. Kretsch, Adam J. Simpkin, Thomas Mulvaney, Phillip Pham, Ramya Rangan, Fan Bu, Ronan M. Keegan, Maya Topf, Daniel J. Rigden, Zhichao Miao, Eric Westhof
Summary: This study reports the assessment of RNA structure predictions and highlights the performance of traditional methods compared to deep learning approaches. The evaluation, based on modeling and comparison with experimental data, shows that models generated by deep learning were worse than those generated by traditional methods. The study also demonstrates the potential utility of current RNA modeling approaches in RNA nanotechnology and structural biology.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Rachael C. C. Kretsch, Ebbe S. S. Andersen, Janusz M. M. Bujnicki, Wah Chiu, Rhiju Das, Bingnan Luo, Benoit Masquida, Ewan K. S. McRae, Griffin M. M. Schroeder, Zhaoming Su, Joseph E. E. Wedekind, Lily Xu, Kaiming Zhang, Ivan N. N. Zheludev, John Moult, Andriy Kryshtafovych
Summary: The success of the first RNA category of the Critical Assessment of Techniques for Structure Prediction competition relied on experimental structures provided by scientists. In this article, these scientists offer a unique and valuable analysis of the predicted models, highlighting areas for improvement. All 10 RNA-only targets showed predicted structures similar to experimental ones. The prediction of RNA-protein complexes remains the biggest challenge, and considering ensemble models for flexible RNAs is proposed.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Computer Science, Artificial Intelligence
Hannah K. Wayment-Steele, Wipapat Kladwang, Andrew M. Watkins, Do Soon Kim, Bojan Tunguz, Walter Reade, Maggie Demkin, Jonathan Romano, Roger Wellington-Oguri, John J. Nicol, Jiayang Gao, Kazuki Onodera, Kazuki Fujikawa, Hanfei Mao, Gilles Vandewiele, Michele Tinti, Bram Steenwinckel, Takuya Ito, Taiga Noumi, Shujun He, Keiichiro Ishi, Youhan Lee, Fatih Ozturk, King Yuen Chiu, Emin Ozturk, Karim Amer, Mohamed Fares, Eterna Participants, Rhiju Das
Summary: Medicines based on messenger RNA (mRNA) hold immense potential, but their worldwide distribution is limited by their thermostability. Predicting the degradation of RNA molecules is crucial for designing more stable RNA therapeutics. A crowdsourced machine learning competition achieved satisfactory results and supported its application in designing stable RNA drugs.
NATURE MACHINE INTELLIGENCE
(2022)
Meeting Abstract
Biophysics
Siyuan Du, Rachael C. Kretsch, Jacob Parres-Gold, Daniel A. Penaherrera, Filip Yabukarski, Margaux M. Pinney, Dan Herschlag
BIOPHYSICAL JOURNAL
(2022)