Article
Microbiology
Jia Liu, Paul Villanueva, Jinlyung Choi, Santosh Gunturu, Yang Ouyang, Lisa K. Tiemann, James R. Cole, Kathryn R. Glanville, Steven J. Hall, Marshall D. McDaniel, Jaejin Lee, Adina Howe
Summary: MetaFunPrimer is a bioinformatic pipeline developed to design primers for numerous genes of interest, enabling gene target prioritization based on their presence and abundance in defined reference genomes. The primers designed by this tool improve the characterization and quantification of functional genes, allowing for a quick and affordable assessment of functional gene abundance and microbial community dynamics using high-throughput PCR methods.
Article
Multidisciplinary Sciences
Huaping Zeng, Kexin Chen, Chouxian Ma, Biyin Zhu, Jun Chuan, Shuan Zhang, Lin Tang, Ting Yang, Zhaohui Sun, Xingkun Yang, Yu Wang
Summary: PrimerScore2 is a robust tool capable of designing primers for multiple PCR variants, evaluating primer specificity by predicting the efficiencies of all target/non-target products.
SCIENTIFIC REPORTS
(2022)
Review
Agricultural Engineering
Aravind Madhavan, K. B. Arun, Parameswaran Binod, Ranjna Sirohi, Ayon Tarafdar, R. Reshmy, Mukesh Kumar Awasthi, Raveendran Sindhu
Summary: Enzyme engineering plays a crucial role in improving the efficiency and stability of enzymes in industrial processes. Protein engineers focus on studying the design and application of enzyme engineering to tailor industrially important enzymes for versatile production of biochemicals.
BIORESOURCE TECHNOLOGY
(2021)
Article
Biochemical Research Methods
Alessandro Pedretti, Angelica Mazzolari, Silvia Gervasoni, Laura Fumagalli, Giulio Vistoli
Summary: This article provides an overview of the latest release of the VEGA suite of programs, which has been developed and freely released for the past 20 years, gaining about 22,500 registered users. In addition to drug design studies, VEGA package also includes cheminformatics and modeling features for various computational chemistry contexts. The flexible architecture of VEGA program allows for expansion and customization, with a focus on the highly optimized HyperDrive library.
Article
Biochemical Research Methods
Ahmed Hafez, Ricardo Futami, Amir Arastehfar, Farnaz Daneshnia, Ana Miguel, Francisco J. Roig, Beatriz Soriano, Jaume Perez-Sanchez, Teun Boekhout, Toni Gabaldon, Carlos Llorens
Summary: SeqEditor is an interactive software tool for nucleotide and protein sequence analysis, featuring a graphical user interface and optimized for managing large sequences and complex datasets. It includes tools for PCR primer design, annotation file management, and content mining from reference genomes.
Article
Biochemical Research Methods
Jeongmin Bae, Hajin Jeon, Min-Soo Kim
Summary: The study introduces a GPU-based pipeline for primer design (GPrimer), significantly improving the speed of primer design by exploiting the computational power of GPUs. GPrimer achieves a notable speedup compared to MRPrimer for the human RefSeq database.
BMC BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
Lin Yang, Feng Ding, Qiang Lin, Junhua Xie, Wei Fan, Fangyin Dai, Peng Cui, Wanfei Liu
Summary: PMPrimer is an automated tool for designing and evaluating multiplex PCR primer pairs for specific targets. It uses statistical filtering and multiple sequence alignment to design optimal primer pairs, and evaluates them based on template coverage, taxon specificity, and target specificity. PMPrimer showed outstanding performance and adaptability compared to existing tools.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Yuru Wang, Christopher D. Katanski, Christopher Watkins, Jessica N. Pan, Qing Dai, Zhuoxun Jiang, Tao Pan
Summary: A high-throughput screening method was introduced to evaluate AlkB variants for demethylation activity on RNA and DNA substrates, leading to the identification of variants with improved activity. This method provides a tool for in vitro evolution of any demethylase enzyme.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Sarah R. Messenger, Edward M. R. Mcguinniety, Luke J. Stevenson, Jeremy G. Owen, Gregory L. Challis, David F. Ackerley, Mark J. Calcott
Summary: Researchers have developed an evolution-inspired method to generate diverse nonribosomal peptides by amplifying and substituting domains from soil metagenomic DNA.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jiajia Che, Kai Wu, Wei Hu, Jinlong Yang
Summary: In this study, an inverse design approach was employed to discover two-dimensional materials with both ferroelectricity and the Rashba effect. Through high-throughput calculations and material screening, 14 specific two-dimensional ferroelectric Rashba semiconductors were identified, which offer potential for electrically reversible spin texture. This finding holds significance for future spintronics.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biotechnology & Applied Microbiology
Christian Sudfeld, Michal Hubacek, Daniel Figueiredo, Mihris I. S. Naduthodi, John van der Oost, Rene H. Wijffels, Maria J. Barbosa, Sarah D'Adamo
Summary: Nannochloropsis oceanica is a promising microalga platform, but current lipid yields are too low for economic feasibility. This study aimed to discover genes associated with increased neutral lipid content, with a promising mutant (HLM23) showing increased lipid content, enhanced photosynthetic performance, and no growth impairment. Transcriptome analysis revealed upregulation of genes related to fatty acid biosynthesis, glycolysis, and the Calvin-Benson-Bassham cycle in HLM23. Insights gained from this study can be used for future genetic engineering strategies to improve lipid productivity of Nannochloropsis.
METABOLIC ENGINEERING
(2021)
Article
Energy & Fuels
Shubhanvit Mishra, Yi-Ju Liu, Chi-Shuo Chen, Da-Jeng Yao
Summary: Microalgae are important green energy resources with high efficiency in fixing carbon dioxide, and are commonly used for biofuel production. This study developed a microfluidic platform for optimizing biofuel production of microalgae, utilizing hanging-drop microfluidic chips fabricated with a cheap CNC micro-milling technique. By culturing Botryococcus braunii in parallel on these chips, and introducing UV-induced mutations, the lipid content of the microalgae was enhanced, showing increased growth and lipid production. This hanging-drop microfluidic system has the potential to facilitate microalgae mutation breeding and cultivation optimization.
Article
Biology
Hidehiko Kawai, Ren Iwata, Shungo Ebi, Ryusei Sugihara, Shogo Masuda, Chiho Fujiwara, Shingo Kimura, Hiroyuki Kamiya
Summary: This study presents an advanced method for mutation analysis using the supF gene. The method is simple, versatile, and cost-effective, and provides valuable insights into mutation frequencies and spectra. The results reveal previously undetected mutations and offer a novel perspective on the mechanisms of mutagenesis.
Article
Biochemistry & Molecular Biology
Signe Christensen, Camille Wernersson, Ingemar Andre
Summary: Characterizing the effects of mutations on stability is critical for understanding the function and evolution of proteins and improving their biophysical properties. A multiplex assay for high throughput screening of protein folding was developed, which can identify stabilizing mutations with a low false positive rate. This method can be combined with functional screens to identify mutations that improve both stability and activity.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Rui Feng, Chuan Zhang, Michael C. Gao, Zongrui Pei, Fan Zhang, Yan Chen, Dong Ma, Ke An, Jonathan D. Poplawsky, Lizhi Ouyang, Yang Ren, Jeffrey A. Hawk, Michael Widom, Peter K. Liaw
Summary: The study introduces a high-throughput computational method to design precipitation-strengthened lightweight high-entropy alloys for elevated-temperature applications. By integrating experimental and theoretical understanding, the accuracy of the thermodynamic database is improved, accelerating the discovery of advanced structural materials. This approach proves to be efficient and useful in screening promising high-entropy alloys for high-temperature applications.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Alexander S. Hauser, Albert J. Kooistra, Christian Munk, Franziska M. Heydenreich, Dmitry B. Veprintsev, Michel Bouvier, M. Madan Babu, David E. Gloriam
Summary: The study identified molecular mechanistic maps of G-protein-coupled receptor activation in humans, revealing structural differences between different classes and laying the foundation for receptor-function studies and drug development.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Clare. R. Harwood, David A. Sykes, Bradley L. Hoare, Franziska M. Heydenreich, Romez Uddin, David R. Poyner, Stephen J. Briddon, D. B. Veprintsev
Summary: The study demonstrated the isolation of beta 2-adrenoceptor (beta 2AR) using a polymer, diisobutylene maleic acid (DIBMA), which showed improved functional and thermal stability compared to traditional detergent methods. This unique method offers significant advantages for biophysical studies of beta 2AR.
Meeting Abstract
Biochemistry & Molecular Biology
John Janetzko, Ryoji Kise, Benjamin Barsi-Rhyne, Dirk H. Siepe, Franziska M. Heydenreich, Matthieu Masureel, Kouki Kawakami, K. C. Garcia, Mark von Zastrow, Asuka Inoue, Brian K. Kobilka
Article
Multidisciplinary Sciences
Janik B. Hedderich, Margherita Persechino, Katharina Becker, Franziska M. Heydenreich, Torben Gutermuth, Michel Bouvier, Moritz Buenemann, Peter Kolb
Summary: Researchers computationally describe alternative allosteric pockets in G-protein-coupled receptors, identifying nine previously untargeted sites for synthetic ligands. They further investigate the potential of modulating receptor function through ligand binding to these sites.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Franziska Marie Heydenreich, Bianca Plouffe, Aurelien Rizk, Dalibor Milic, Joris Zhou, Billy Breton, Christian Le Gouill, Asuka Inoue, Michel Bouvier, Dmitry B. Veprintsev
Summary: By modeling G protein activation as a Michaelis-Menten reaction, we have developed a novel method for quantifying signaling bias. V2R activates, or at least engages, G proteins from all G protein subfamilies, including Gi2, Gz, Gq, G12, and G13. Their relative activation may explain its Gs-independent signaling.
MOLECULAR PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
David A. Sykes, Mireia Jimenez-Roses, John Reilly, Robin A. Fairhurst, Steven J. Charlton, Dmitry B. Veprintsev
Summary: This study investigates the binding kinetics of several clinically relevant beta(1/2)-adrenoceptor agonists and antagonists. The results show that hydrophobic properties directly affect the association rate and affinity for the beta(1) adrenoceptor. The study also reveals the potential role of kinetics in the pharmacology of clinically used beta-blockers. Additionally, the findings suggest that hydrophobic interactions dominate the kinetics of ligand binding in the beta(1) adrenoceptor, while a combination of hydrophobicity and negative charge attracts ligands to the surface of the beta(2) adrenoceptor, promoting ligand binding kinetics.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2022)
Article
Pharmacology & Pharmacy
Mireia Jimenez-Roses, Bradley Angus Morgan, Maria Jimenez Sigstad, Thuy Duong Zoe Tran, Rohini Srivastava, Asuman Bunsuz, Leire Borrega-Roman, Pattarin Hompluem, Sean A. Cullum, Clare R. Harwood, Eline J. Koers, David A. Sykes, Iain B. Styles, Dmitry B. Veprintsev
Summary: This study uses machine learning techniques to investigate the interactions between ligands and G protein-coupled receptors (GPCRs), identifying key interactions associated with agonist and antagonist activity. This approach provides valuable insights for the drug discovery process.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2022)
Article
Pharmacology & Pharmacy
Sean A. Cullum, Dmitry B. Veprintsev, Stephen J. Hill
Summary: This study analysed the kinetic phases of cAMP responses to beta(2)-adrenoceptor agonists in HEK293 cells expressing low levels of endogenous beta(2)-adrenoceptor. It was found that partial agonists had reduced relative IRmax values compared to isoprenaline. Preincubation with beta(2)-adrenoceptor antagonists led to a decrease in the peak response and exacerbated the effect on IRmax values. These findings provide insights into the hemi-equilibria in low receptor reserve systems with agonist-antagonist interactions.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
John Janetzko, Ryoji Kise, Benjamin Barsi-Rhyne, Dirk H. Siepe, Franziska M. Heydenreich, Kouki Kawakami, Matthieu Masureel, Shoji Maeda, K. Christopher Garcia, Mark von Zastrow, Asuka Inoue, Brian K. Kobilka
Summary: This study reveals the role of membrane phosphoinositides (PIPs) in β-arrestin recruitment and GPCR-β-arrestin complex dynamics through cell-based and in vitro biophysical assays. GPCRs are classified into two groups, with one requiring PIP binding for β-arrestin recruitment and the other not. Plasma membrane PIPs enhance the active conformation of β-arrestin and stabilize GPCR-β-arrestin complexes by promoting a fully engaged state. As allosteric modulators of GPCR-β-arrestin complex dynamics, membrane PIPs allow for additional conformational diversity beyond GPCR phosphorylation alone. For GPCRs that require membrane PIP binding for β-arrestin recruitment, this provides a mechanism for rapid β-arrestin release upon GPCR translocation to endosomes, enabling its quick recycling.
Article
Multidisciplinary Sciences
Justine S. Paradis, Xiang Feng, Brigitte Murat, Robert E. Jefferson, Badr Sokrat, Martyna Szpakowska, Mireille Hogue, Nick D. Bergkamp, Franziska M. Heydenreich, Martine J. Smit, Andy Chevigne, Michel Bouvier, Patrick Barth
Summary: This article presents a computational approach for predicting receptor self-associations and designing receptor oligomers with various quaternary structures and signaling properties. Using this approach, the chemokine receptor CXCR4 dimers were successfully designed to have different conformations and abilities to activate distinct intracellular signaling proteins. The study also revealed the existence of a bias switch at the dimer interface of several G protein-coupled receptors, including CXCR4, mu-Opioid, and type-2 Vasopressin receptors, that selectively control the activation of G proteins vs beta-arrestin-mediated pathways.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Miroslav Kosar, David A. Sykes, Alexander E. G. Viray, Rosa Maria Vitale, Roman C. Sarott, Rudolf L. Ganzoni, David Onion, Janelle M. Tobias, Philipp Leippe, Christoph Ullmer, Elisabeth A. Zirwes, Wolfgang Guba, Uwe Grether, James A. Frank, Dmitry B. Veprintsev, Erick M. Carreira
Summary: The study presents a novel ligand-directed covalent labeling strategy for visualizing and studying CB2R, a promising target for the treatment of neuroinflammatory disorders. The selective covalent labeling of CB2R was achieved using fluorogenic probes, and the probes were successfully applied to visualize CB2R in live cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Thais Gazzi, Benjamin Brennecke, Kenneth Atz, Claudia Korn, David Sykes, Gabriel Forn-Cuni, Patrick Pfaff, Roman C. Sarott, Matthias Westphal, Yelena Mostinski, Leonard Mach, Malgorzata Wasinska-Kalwa, Marie Weise, Bradley L. Hoare, Tamara Miljus, Maira Mexi, Nicolas Roth, Eline J. Koers, Wolfgang Guba, Andre Alker, Arne C. Rufer, Eric A. Kusznir, Sylwia Huber, Catarina Raposo, Elisabeth A. Zirwes, Anja Osterwald, Anto Pavlovic, Svenja Moes, Jennifer Beck, Matthias Nettekoven, Irene Benito-Cuesta, Teresa Grande, Faye Drawnel, Gabriella Widmer, Daniela Holzer, Tom van der Wel, Harpreet Mandhair, Michael Honer, Jurgen Fingerle, Joerg Scheffel, Johannes Broichhagen, Klaus Gawrisch, Julian Romero, Cecilia J. Hillard, Zoltan V. Varga, Mario van der Stelt, Pal Pacher, Jurg Gertsch, Christoph Ullmer, Peter J. McCormick, Sergio Oddi, Herman P. Spaink, Mauro Maccarrone, Dmitry B. Veprintsev, Erick M. Carreira, Uwe Grether, Marc Nazare
Summary: This study reports the development of a novel fluorescent CB2R agonist probe that can detect CB2R in living cells and zebrafish larvae. These findings contribute to the clinical translatability of CB2R-based drugs.
