Article
Chemistry, Physical
Mikita M. Misiura, Alexander M. Berezhkovskii, Sergey M. Bezrukov, Anatoly B. Kolomeisky
Summary: Trapping by active sites on surfaces plays important roles in various chemical and biological processes, but existing theoretical descriptions do not fully account for the role of surfaces. Surface diffusion is found to be crucial in mediating trapping by active sites.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Chemistry, Physical
Goro Nishide, Keesiang Lim, Mahmoud Shaaban Mohamed, Akiko Kobayashi, Masaharu Hazawa, Takahiro Watanabe-Nakayama, Noriyuki Kodera, Toshio Ando, Richard W. Wong
Summary: The study utilized high-speed atomic force microscopy to observe dynamic DNA-histone H2A interactions, revealing different conformations on different substrates and observing reversible liquid-liquid phase separation of DNA-H2A aggregates.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Biology
Jee Min Kim, Pat Visanpattanasin, Vivian Jou, Sheng Liu, Xiaona Tang, Qinsi Zheng, Kai Yu Li, Jonathan Snedeker, Luke D. Lavis, Timothee Lionnet, Carl Wu
Summary: Conserved ATP-dependent chromatin remodelers exhibit hyperkinetic behaviors in chromatin with notably fast dissociation kinetics, requiring ATP binding or hydrolysis for enhanced dynamics. Multiple remodelers can repeatedly occupy the same promoter region on a timescale of minutes, suggesting an ongoing 'tug-of-war' that controls a shifting window of accessibility for the transcription initiation machinery.
Article
Management
T. Boettger, V Grimm, T. Kleinert, M. Schmidt
Summary: The liberalized gas markets in Europe are organized as entry-exit regimes, decoupling gas trade and transport. The study reveals significant welfare losses due to unused network capacity as a result of feasibility requirements for technical capacities, with network structure playing a crucial role in the optimal choice of technical capacities.
EUROPEAN JOURNAL OF OPERATIONAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Elisa Oberbeckmann, Nils Krietenstein, Vanessa Niebauer, Yingfei Wang, Kevin Schall, Manuela Moldt, Tobias Straub, Remo Rohs, Karl-Peter Hopfner, Philipp Korber, Sebastian Eustermann
Summary: This study reveals how chromatin remodelers determine nucleosome positioning through reading DNA shape/mechanics information and interacting with DNA sequence-specific binding sites. The findings suggest that DNA shape/mechanics play a crucial role in nucleosome organization.
NATURE COMMUNICATIONS
(2021)
Article
Engineering, Marine
Xu Wang, Xujian Lyu
Summary: The experiment investigates the cavity dynamics and trajectories of twin spheres vertically entering water side-by-side at different time intervals and lateral distances. The results show that the interaction between the spheres changes with the increase of time interval and lateral distance, affecting the motion characteristics of the second water-entry sphere.
Article
Multidisciplinary Sciences
Yunhui Peng, Shuxiang Li, Alexey Onufriev, David Landsman, Anna R. Panchenko
Summary: This study investigates the roles of histone tails in nucleosomal DNA binding using molecular dynamics simulations, revealing specific binding modes for different types of histone tails and the impact of modifications on interactions. Charge-altering modifications suppress tail-DNA interactions and enhance interactions between nucleosomes and nucleosome-binding proteins.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Shingo Hirashima, Soyoung Park, Hiroshi Sugiyama
Summary: Forster resonance energy transfer (FRET) is a useful tool for understanding biomolecular dynamics, and FRET-based analysis of nucleosomes has the potential to bridge the gap between static structures and dynamic cellular behaviors. Nucleoside-based FRET pairs offer advantages over traditional pairs, as they can be incorporated into the helical structures of nucleic acids. This study investigates the construction of nucleosomes with nucleobase FRET pairs and analyzes experimental and theoretical FRET efficiencies using fluorescence spectroscopy and molecular dynamics simulations, respectively. The results show distinguishable experimental FRET efficiencies depending on the positions of FRET pairs in nucleosomal DNA, which are supported by theoretical calculations. This research suggests the possibility of using this approach to analyze structural changes in nucleosomes caused by epigenetic modifications or internucleosomal interactions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Physical
Le Qiao, Maxime Ignacio, Gary W. Slater
Summary: By introducing an efficient Kinetic Monte Carlo algorithm to simulate the capture process by a nanopore, we are able to study time-dependent processes such as transients. Simulation results show that the steady-state depletion zone near the pore narrows at higher field intensities and a second depletion region can propagate inward from the outer wall in a finite sample reservoir. The flatness of the electric field near the pore induces a traffic jam that can significantly increase the transient time.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Leehyeon Kim, Byung-Gil Lee, Minki Kim, Min Kyung Kim, Do Hoon Kwon, Hyunmin Kim, Heike Broetz-Oesterhelt, Soung-Hun Roh, Hyun Kyu Song
Summary: ClpP serine peptidase is a tetradecameric degradation molecular machine involved in many physiological processes, being activated by ADEPs without ATPases and showing potential as novel antibiotics. Structural and cryo-electron microscopy studies have revealed different conformational states of ClpP under various pH conditions, providing insight into the molecular mechanism of product release.
Article
Multidisciplinary Sciences
Yilong Feng, Zexue He, Zhenyu Luo, Francesco Rota Sperti, Ibai E. Valverde, Wenli Zhang, David Monchaud
Summary: The search for G-quadruplex (G4) sequences is driven by their involvement in cellular processes and genetic diseases. Sequencing-based methods have been developed to detect G4s in DNA (in vitro) and fixed chromatin (in vivo). A new technique called G4-RNA precipitation and sequencing (G4RP-seq) has been developed to assess the prevalence of RNA G4s transcriptome wide. This study compares the efficiency of G4DP-seq and BG4-DNA-IP-seq in mapping DNA G4s in rice, using small molecule ligands and the BG4 antibody.
Article
Communication
Yulong Chen, Liyuan Ma, Peter F. Orazem
Summary: Broadband access has varying effects on establishment entry and exit across industries and markets. Overall, broadband encourages entry and reduces exit. Both urban and rural markets experience net entry due to broadband entry. The effects of broadband differ by sector, with construction and professional services having establishment gains in both urban and rural markets. Finance and insurance, real estate, information, and arts and entertainment sectors only have net establishment gains in urban markets. Urban retail and rural manufacturing and hospitality sectors experience net establishment losses. Broadband also leads to a net reallocation of educational services establishments from rural to urban areas.
TELECOMMUNICATIONS POLICY
(2023)
Article
Chemistry, Multidisciplinary
Yan-Ni Zhang, Yuwei Zhang, Shan Su, Han-Ying Zhu, Wei Xu, Lu Wang, Meng Wu, Kai Chen, Fei-Qiang Yu, Tong-Kuai Xi, Qin Zhou, You-Hua Xie, Ximing Qin, Honghua Ge, Lu Lu, Jie Qing, Ge-Min Fang
Summary: The study introduces a dimeric ACE2 peptide mimetic with high binding affinity for SARS-CoV-2 spike RBD, capable of inhibiting the virus in cell cultures. It offers insights for optimizing peptide-based anti-SARS-CoV-2 inhibitors.
CHEMICAL COMMUNICATIONS
(2022)
Article
Engineering, Ocean
Xi Yang, Song Feng, Jinxin Wu, Guiyong Zhang, Guangqi Liang, Zhifan Zhang
Summary: In this paper, the adaptive particle refinement and particle shifting technique are coupled and applied to investigate the process of water entry and exit. Comprehensive analysis of different coupled schemes is conducted and the numerical model is verified by benchmark tests, showing stability and accuracy.
APPLIED OCEAN RESEARCH
(2023)
Article
Energy & Fuels
Yubing Gao, Qiukai Gai, Xun Xi, Xingxing Zhang, Manchao He
Summary: This paper proposes a machine learning-based method for predicting the stability of gob-side entry formation in coal mining. The method combines artificial neural networks with particle swarm optimization or genetic optimization algorithms. The results show that the method has high predictive accuracy and sensitivity analysis reveals the most important parameters for entry stability. This method provides a practical tool for stability prediction and design optimization.
ENERGY SCIENCE & ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Desmarini Desmarini, Daniel Truong, Lorna Wilkinson-White, Chandrika Desphande, Mario Torrado, Joel P. Mackay, Jacqueline M. Matthews, Tania C. Sorrell, Sophie Lev, Philip E. Thompson, Julianne Teresa Djordjevic
Summary: New antifungals are urgently needed to treat invasive fungal infections. The fungal inositol polyphosphate kinase (IPK) pathway is a promising target. TNP and its analogues show inhibitory effects on IP3-4K from C. neoformans.
Article
Infectious Diseases
Caitlin Keighley, Antoine M. van Oijen, Stuart J. Brentnall, Martina Sanderson-Smith, Peter Newton, Spiros Miyakis
Summary: The study found similar trends in antimicrobial resistance (AMR) among urinary Escherichia coli isolates from a private community-based laboratory and a public hospital-based laboratory in an Australian local health district. AMR rates increased over time in both settings, with consistently higher rates in the public hospital-based laboratory. Interventions targeting the community-based laboratory setting are crucial for addressing AMR in the community.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)
Article
Multidisciplinary Sciences
Nicholas R. Marzano, Bishnu P. Paudel, Antoine M. van Oijen, Heath Ecroyd
Summary: The study used total internal reflection fluorescence (TIRF) microscopy and single-molecule fluorescence resonance energy transfer (smFRET) to observe the folding process of firefly luciferase proteins mediated by the bacterial Hsp70 system. The researchers found that there are multiple cycles of chaperone binding and release to individual clients during refolding, and high rates of chaperone cycling improve refolding yield. Additionally, they discovered that DnaJ remodels misfolded proteins through a conformational selection mechanism, while DnaK resolves misfolded states through mechanical unfolding. This study elucidates important mechanistic details of chaperone-assisted folding that are inaccessible using other methods.
Article
Biochemical Research Methods
Poanna Tran, Hue N. T. Tran, Kirsten L. McMahon, Jennifer R. Deuis, Lotten Ragnarsson, Alexander Norman, Simon J. Sharpe, Richard J. Payne, Irina Vetter, Christina I. Schroeder
Summary: This study aimed to design new bivalent inhibitors of Na(V)1.7 by combining the pore blocking activity of conotoxins with the gating modifier activity of spider toxins. The potency and selectivity of the resulting bivalent toxins were evaluated by ligating a conotoxin to a spider toxin. The bivalent peptide Pro[LPATG(6)]Sx, resulting from the ligation of ProTx-II and SxIIIC, showed the best combination with conserved potency at hNa(V)1.7.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Kasuni B. Ekanayake, Mithun C. Mahawaththa, Haocheng Qianzhu, Elwy H. Abdelkader, Josemon George, Sven Ullrich, Rhys B. Murphy, Sarah E. Fry, Jason Johansen-Leete, Richard J. Payne, Christoph Nitsche, Thomas Huber, Gottfried Otting
Summary: N6-(((trimethylsilyl)-methoxy)carbonyl)-L-lysine (TMSK) and N6-trifluoroacetyl-L-lysine (TFAK) are non-canonical amino acids that can be incorporated into proteins via genetic encoding. A new aminoacyl-tRNA synthetase specific for N6-(((trimethylsilyl)methyl)-carbamoyl)-L-lysine (TMSNK) is described, which is chemically more stable than TMSK. The study demonstrates the use of these amino acids for site-specific NMR analysis of ligand binding to large proteins of limited stability and at low concentrations.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Hue N. T. Tran, Elena Budusan, Natalie J. Saez, Alexander Norman, Isaac J. Tucker, Glenn F. King, Richard J. Payne, Lachlan D. Rash, Irina Vetter, Christina I. Schroeder
Summary: Hi1a is a naturally occurring bivalent spider-venom peptide that shows promise for limiting ischemic damage. However, challenges in synthesizing and producing the peptide in large quantities have hindered progress in this area. Access to synthetic Hi1a is crucial for its development as a pharmacological tool and potential therapeutic.
Article
Multidisciplinary Sciences
Tara K. Bartolec, Xabier Vazquez-Campos, Alexander Norman, Clement Luong, Marcus Johnson, Richard J. Payne, Marc R. Wilkins, Joel P. Mackay, Jason K. K. Low
Summary: Significant advances in cryoelectron microscopy have expanded our ability to create structural models of proteins and protein complexes. Cross-linking mass spectrometry (XL-MS) is demonstrated to be a powerful tool for high-throughput experimental assessment of protein structures and interactions. The combination of XL-MS data with AlphaFold2 predictions offers opportunities to explore the structural proteome and interactome in depth.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Organic
Arthur H. Tang, Richard J. Payne
Summary: Gallinamide A, a natural product produced by cyanobacteria, shows potent anti-parasitic activity by inhibiting essential cysteine protease enzymes. It has also been found to possess strong antiviral activity against SARS-CoV-2 by covalently inhibiting the host cysteine protease cathepsin L involved in viral entry. To conduct detailed pre-clinical studies on its potential as a COVID-19 antiviral, a more efficient synthetic route was developed to obtain significant quantities of this natural product. The second generation total synthesis of Gallinamide A described here delivered the compound in a yield of 32% on a 315 mg scale over 16 steps (9 steps in the longest linear sequence).
Review
Chemistry, Multidisciplinary
Katriona Harrison, Angus S. Mackay, Lucas Kambanis, Joshua W. C. Maxwell, Richard J. Payne
Summary: The homochirality of biomolecules in nature has been crucial for the existence of life and has also provided opportunities for synthetic chemists to generate molecules with inverted chirality. Recent work on synthetic mirror-image proteins, using modern synthetic strategies, has led to their applications in protein crystallography, drug discovery, and the creation of mirror-image life.
NATURE REVIEWS CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Clara Bersi Motta Correa, Ana Carolina Kogawa, Marlus Chorilli, Herida Regina Nunes Salgado
Summary: Tyrosine sulfation is a post-translational modification that plays a crucial role in modulating the function of salivary proteins from blood feeding organisms. Utilizing synthetic chemistry, homogeneously sulfated peptides and proteins have been generated to study their structure and function. This research has provided valuable insights into the importance of tyrosine sulfate in enhancing anticoagulant activity.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Oliver H. Rathje, Lara Perryman, Richard J. Payne, Dieter W. Hamprecht
Summary: In this study, a novel approach called PROteolysis TArgeting Chimeras (PROTACs) was developed to effectively degrade MLKL and completely inhibit cell death. This work demonstrates the feasibility of targeting MLKL using a PROTAC approach and provides a powerful tool to further understand the role of MLKL within the necroptotic pathway.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Shankar Raj Devkota, Pramod Aryal, Rina Pokhrel, Wanting Jiao, Andrew Perry, Santosh Panjikar, Richard J. Payne, Matthew C. J. Wilce, Ram Prasad Bhusal, Martin J. Stone
Summary: This study focused on a type of chemokine-binding proteins called A3 evasins from tick saliva, which can bind with CC chemokines and inhibit their receptor activation. Structure-based modifications of A3 evasins can alter their chemokine selectivity, suggesting their potential applications in targeted anti-inflammatory therapy.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Kasuni B. Ekanayake, Mithun C. Mahawaththa, Haocheng Qianzhu, Elwy H. Abdelkader, Josemon George, Sven Ullrich, Rhys B. Murphy, Sarah E. Fry, Jason Johansen-Leete, Richard J. Payne, Christoph Nitsche, Thomas Huber, Gottfried Otting
Summary: TMSK, TMSNK, and TFAK are non-canonical amino acids that can be incorporated into proteins through genetic encoding. A new aminoacyl-tRNA synthetase specific for TMSNK is described, which is chemically more stable. Using the SARS-CoV-2 main protease (Mpro) as a model system, intense signals in the nuclear magnetic resonance (NMR) spectrum were observed for the trimethylsilyl and CF3 groups. The response of these groups to active-site ligands differed depending on their proximity to the active site, and the previously reported binding site of the ligand pelitinib was not confirmed.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Cameron C. Hanna, Joshua W. C. Maxwell, Hendra S. Ismanto, Anneliese S. Ashhurst, Lukas M. Artner, Santosh Rudrawar, Warwick J. Britton, Sho Yamasaki, Richard J. Payne
Summary: The covalent fusion of immunostimulatory adjuvants to immunogenic antigens is a promising strategy for the development of effective synthetic vaccines for infectious diseases. This article describes the conjugation of a mycobacterial peptide antigen ESAT6 to a potent glycolipid adjuvant TDB targeting Mincle.
CHEMICAL COMMUNICATIONS
(2022)
