Article
Chemistry, Multidisciplinary
Guangzhong Ma, Zijian Wan, Yunze Yang, Wenwen Jing, Shaopeng Wang
Summary: This study introduces a plasmonic imaging technique that enables precise 3D tracking of surface-tethered single particles in real time, with applications in studying DNA-enzyme interactions. The analysis of particle motion patterns allows for the identification of specific and nonspecific interactions in immunoassays, contributing to the understanding of molecular dynamics and interactions at the single-molecule level.
Article
Chemistry, Physical
Aisha Ahsan, Luiza Buimaga-Iarinca, Thomas Nijs, Sylwia Nowakowska, Sk Rejaul, S. Fatemeh Mousavi, Mehdi Heydari, Meike Stoehr, Sameena S. Zaman, Cristian Morari, Lutz H. Gade, Thomas A. Jung
Summary: Host-guest architectures provide ideal systems for investigating site-specific physical and chemical effects. In this study, we found that the symmetry, registry, lateral packing, and adsorption height of small clusters formed upon condensation are modified by the presence of cycloalkanes in confined spaces. While cyclopentane and cycloheptane show cooperativity upon filling, cyclooctane and to a lesser degree cyclohexane redistribute to more favorable adsorption sites. This site-specific modification of interaction and behavior is crucial for applications of porous materials in gas storage or catalysis.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Computer Science, Artificial Intelligence
Yiyuan Fang, Shuyi Deng, Cai Li
Summary: This study presents a deep learning framework, Mutation Rate Learner (MuRaL), to predict mutation rates at the nucleotide level using genomic sequences as input. The results demonstrate that MuRaL outperforms current state-of-the-art methods in predictive performance and can build models with few training mutations and individuals, leveraging transfer learning to reduce data and time demands. MuRaL is applied to generate genome-wide mutation rate maps for representative species and used to stratify human genes into different functional groups based on improved mutation rate estimates.
NATURE MACHINE INTELLIGENCE
(2022)
Article
Chemistry, Multidisciplinary
Muhammad Ghufran Rafique, Jacob M. M. Remington, Finley Clark, Haochen Bai, Violeta Toader, Dmytro F. F. Perepichka, Jianing Li, Hanadi F. F. Sleiman
Summary: The study focuses on the systematic research of polymer structure, pathway mechanism, and supramolecular morphology in order to assemble water-soluble block copolymers into two-dimensional structures. By using sequence-defined triblock DNA amphiphiles, the researchers successfully polymerized free-standing DNA nanosheets in water. They found that the alkyl chain core formed a cell membrane-like structure, and the distal pi-stacking chromophore block folded back to interact with the hydrophilic DNA block on the nanosheet surface. This interaction was crucial for sheet formation and showed sensitivity to DNA sequence. The findings open up possibilities for applications in cell sensing, nucleic acid therapeutic delivery, and enzyme arrays.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Analytical
Loredana Mereuta, Alina Asandei, Isabela Dragomir, Jonggwan Park, Yoonkyung Park, Tudor Luchian
Summary: This study introduces an exploratory single-molecule approach for multiplexed discrimination among similar-sized single-stranded DNAs by combining short arginine tags with peptide nucleic acid probes and alpha-hemolysin nanopore. The detection of ssDNA targets was enabled by distinctive molecular processes associated with nanopore-mediated duplexes capture, trapping, and unzipping, marked by the length-variable poly-Arg tail.
ANALYTICAL CHEMISTRY
(2022)
Article
Biology
Jixue Sun, Fei Liu, Longxiao Yuan, Ning-Ning Pang, Bing Zhu, Na Yang
Summary: This study elucidates the activation mechanism of DNMT1 using various sampling methods. The results show that the binding of H3Ub2 to the RFTS domain of DNMT1 leads to conformational changes, activating DNMT1.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Article
Ecology
Shimon Bershtein, Daniel Kleiner, Dan Mishmar
Summary: Recent advances in AI-based 3D protein structure prediction have the potential to address health-related questions and impact evolution. Integration of structural predictions with functional genomic studies is emphasized for a comprehensive understanding of protein properties and their effects on fitness.
NATURE ECOLOGY & EVOLUTION
(2021)
Article
Chemistry, Physical
Ayari Miyajima, Hiroyuki Nakao, Keisuke Ikeda, Minoru Nakano
Summary: Biological membranes approach each other in various biological phenomena, leading to changes in the interbilayer space and lipid dynamics. By using static and dynamic small-angle neutron scattering, we investigated the structure and dynamics of vesicles aggregated due to depletion attraction caused by polyethylene glycol (PEG). Manipulating the interbilayer distance using PEG-conjugated lipids revealed rapid lipid transfer between vesicles when the opposing bilayers were within -2 nm of each other, a region where water molecules were more structured. Kinetic analysis suggested that the decrease in water entropy drove the lipid transfer. These findings contribute to understanding the dynamic function of biomembranes in confined regions.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Israel Serrano-Chacon, Bartomeu Mir, Lorenzo Cupellini, Francesco Colizzi, Modesto Orozco, Nu'ria Escaja, Carlos Gonzalez
Summary: We studied a DNA oligonucleotide that can form two different i-motif structures, with their stability depending on pH and temperature. The structure at neutral pH is stabilized by C:C+ base pairs and G:C:G:C tetrads. At pH 5, a more elongated structure consisting of C:C+ base pairs and G:T:G:T tetrads is observed. The transition between these two structures is driven by the protonation state of key cytosines.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Israel Serrano-Chacon, Bartomeu Mir, Lorenzo Cupellini, Francesco Colizzi, Modesto Orozco, Nuria Escaja, Carlos Gonzalez
Summary: We studied a DNA oligonucleotide that forms two different i-motif structures depending on pH and temperature. At neutral pH, the major structure is stabilized by C:C+ base pairs and G:C:G:C tetrads. At pH 5, a more elongated i-motif structure with C:C+ base pairs and G:T:G:T tetrads is observed. Molecular dynamics calculations showed that the conformational transition between the two structures is driven by the protonation state of key cytosines. This study reveals the pH-dependent plasticity and conformational switch of i-motif structures.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Analytical
Xun Gong, Soo-Yeon Cho, Sydney Kuo, Babatunde Ogunlade, Kathryn Tso, Daniel P. Salem, Michael S. Strano
Summary: Colloidal single-walled carbon nanotubes offer a promising platform for molecular recognition at the nanoscale. By modifying the noncovalent corona phases of the nanotubes, optical sensors can be designed through a phenomenon known as corona phase molecular recognition. In this study, the interactions between dilute divalent metal cations and DNA corona phases were explored, leading to improved experimental conditions for sensing metal ions and the detection of nanomolar levels of mercury ions in fish tissue extract.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jahaun Azadmanesh, Mohamed A. Seleem, Lucas Struble, Nicholas A. Wood, Derek J. Fisher, Jeffrey J. Lovelace, Antonio Artigues, Aron W. Fenton, Gloria E. O. Borgstahl, Scot P. Ouellette, Martin Conda-Sheridan
Summary: Chlamydia trachomatis (CT) is a common bacterial sexually transmitted infection that can cause preventable blindness. The pathogenic bacteria's Caseinolytic proteases (ClpP) are attractive targets for antibiotics, especially against persister colonies with resistance to common antibiotics. The crystal structure of full-length ClpP2 has been determined, providing valuable information for drug design and understanding the activation of ClpP complex within this important human pathogen.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Jae Young Lee, Heeyuen Koh, Do-Nyun Kim
Summary: This study presents a computational framework for analyzing the equilibrium and non-equilibrium dynamics of structured DNA assemblies. The framework successfully simulates the dynamic reconfiguration of DNA structures in response to changes in ion concentration. This research offers a rational method for designing responsive and reconfigurable DNA machines.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Haozhi Sha, Yunpeng Ma, Guoping Cao, Jizhe Cui, Wenfeng Yang, Qian Li, Rong Yu
Summary: Defects in crystals have a significant role in influencing the mechanical, electrical, luminescent, and magnetic behaviors of materials. However, accurately measuring defect structures has been challenging due to symmetry breaking and complex modifications in atomic configuration and crystal tilt at the defects. In this study, deep-sub-angstrom resolution imaging of dislocation cores was achieved using multislice electron ptychography with an adaptive propagator, allowing for sub-nanometer scale mapping of crystal tilt and depth-dependent atomic structure recovery of dislocations. This deep-sub-angstrom resolution and depth-dependent imaging of defects holds great potential for revealing microstructures and properties of real materials and devices.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Juan-Juan Sun, Qi-Yuan Fan, Xin Jin, Jing-Li Liu, Tong-Tong Liu, Bin Ren, Jun Cheng
Summary: This study investigates the dynamic coupling effect of sub-nanometer gold clusters with elementary reactions using ab initio molecular dynamics and free energy calculation. The results reveal that the solid-to-liquid phase transition of cluster catalysts facilitates the reaction process, and different cluster sizes exhibit different transition temperatures, indicating a non-trivial size effect. These findings contribute to the understanding and rational design of cluster catalysts.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Shih-Chi Luo, Hsin-Yi Yeh, Wei-Hsuan Lan, Yi-Min Wu, Cheng-Han Yang, Hao-Yen Chang, Guan-Chin Su, Chia-Yi Lee, Wen-Jin Wu, Hung-Wen Li, Meng-Chiao Ho, Peter Chi, Ming-Daw Tsai
Summary: RAD51 and DMC1 recombinases catalyse high-fidelity and mismatch tolerant recombination, processes that are indispensable for the maintenance of genomic integrity. The study elucidates the structural difference between RAD51 and DMC1 with regard to mismatch tolerance, showing that key residues in Loop 1 and Loop 2 play a crucial role in determining the fidelity of DNA recombinases.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Yi-Yun Lin, Min-Hsuan Li, Yen-Chan Chang, Peng-Yu Fu, Ryosuke L. Ohniwa, Hung-Wen Li, Jing-Jer Lin
Summary: Telomeres are crucial for chromosome maintenance, and Cdc13 is an essential telomeric DNA binding protein that caps telomeres and regulates telomerase function. Research shows that specific binding of Cdc13 on single-stranded telomeric DNA can shorten duplex DNA into distinct states, and this shortening is dynamic and independent of duplex DNA sequences or length. Moreover, the inability of Pif1 helicase to remove Cdc13 from the shortened DNA-Cdc13 complex suggests a structurally stable complex formation through shortening of bound DNA.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Marc-Andre Leblanc, Morgan R. Fink, Thomas T. Perkins, Marcelo C. Sousa
Summary: The study shows that effector proteins from certain bacteria can be injected into host cells through a type III secretion system. These proteins need to be partially unfolded to pass through the narrow channel. Mechanical unfolding of the proteins revealed that they exhibit low force and high mechanical compliance, facilitating efficient secretion.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
David R. Jacobson, Thomas T. Perkins
Summary: By using an atomic-force-microscope assay optimized for mechanical force to reversibly unfold local regions of an individual protein, researchers overcame limitations of chemical denaturation assays in understanding the energetics of membrane proteins. This approach provided quantitative insight into the Delta Delta G of single amino acid mutations in membrane proteins and highlighted the contribution of membrane protein-lipid contacts to folding energetics. The platform established allows for determining Delta Delta G for fully folded membrane proteins embedded in their native bilayers.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Devin T. Edwards, Marc-Andre Leblanc, Thomas T. Perkins
Summary: Single-molecule force spectroscopy was used to study protein folding dynamics, revealing intrinsic changes in protein folding dynamics and transition state height under different pH conditions. Despite differences in destabilization mechanisms, constant-force landscapes showed minimal differences in transition state height, while force-dependent rates increased as pH decreased. This study provides insights for future AFM-based studies of mechanoresponsive proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Christopher Liczner, Cameron C. Hanna, Richard J. Payne, Christopher J. Wilds
Summary: This study presents an efficient method for synthesizing peptide-oligonucleotide conjugates using a diselenide-selenoester ligation strategy, which leads to stable amide linkages between the two biomolecules. The novel conjugation strategy increases synthesis efficiency and expands the applications of chemical modification.
Article
Multidisciplinary Sciences
Kai-Hang Lei, Han-Lin Yang, Hao-Yen Chang, Hsin-Yi Yeh, Dinh Duc Nguyen, Tzu-Yu Lee, Xinxing Lyu, Megan Chastain, Weihang Chai, Hung-Wen Li, Peter Chi
Summary: In response to replication stress, the proteins RPA and CST play a key role in regulating RAD51 activity. While RPA coats single-stranded DNA to prevent RAD51 loading, CST can target and tether RAD51 to RPA-coated ssDNA under high ionic strength conditions, allowing RAD51 to assemble a functional filament and exhibit strand-exchange activity. These findings provide insights into the mechanism of how CST and RPA coordinate to regulate RAD51 during replication stress.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Alexander Pontarelli, Christopher J. Wilds
Summary: This article describes the synthesis of a novel C5-propynyl-beta-Darabinouridine (araUP) phosphoramidite and its incorporation into oligonucleotides. The chemical modification of oligonucleotides can enhance their stability and improve their resistance to nucleases and serum, which shows potential for therapeutic gene silencing.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Organic
Alexander Pontarelli, Jiang Tian Liu, Hourieh Movasat, Sarah Menard, Jung Kwon Oh, Christopher J. Wilds
Summary: The synthesis and incorporation of a tosylated phosphoramidite linker containing a disulfide bond is described. This linker was efficiently incorporated into short DNA and RNA oligomers using automated solid phase synthesis, allowing for the expansion of strategies for bifunctional modification of synthetic oligonucleotides for conjugation applications.
Article
Biochemistry & Molecular Biology
Guennadi Kozlov, Sandy Mattijssen, Jianning Jiang, Samuel Nyandwi, Tara Sprules, James R. Iben, Steven L. Coon, Sergei Gaidamakov, Anne M. Noronha, Christopher J. Wilds, Richard J. Maraia, Kalle Gehring
Summary: In this study, the La-module of LARP1 was characterized, and it was found that unlike other LARPs, the La-module of LARP1 does not contain an RRM domain. The La-module alone is capable of binding poly(A) RNA with high specificity for the RNA 3'-end. This study provides insights into the functional relevance of LARP1 RNA binding in cells.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Alexander Pontarelli, Christopher J. Wilds
Summary: Chemical modifications on nucleic acids have allowed for the development of ASOs in the clinic. In this study, the synthesis and incorporation of C5-propynyl arabinouridine and arabinocytidine into ASOs were reported. The modified ASOs showed improved stability with RNA but not with DNA. This suggests that C5-modified arabinonucleic acids could be a potential chemical modification for therapeutic ASOs.
Article
Biochemistry & Molecular Biology
Chia-Lun Guh, Kai-Hang Lei, Yi-An Chen, Yi-Zhen Jiang, Hao-Yen Chang, Hungjiun Liaw, Hung-Wen Li, Hsin-Yung Yen, Peter Chi
Summary: This study provides evidence for an unknown function of RAD51 paralogs in synergizing with RAD51 nucleoprotein filament to prevent degradation of stressed replication forks.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Wei Lee, Hiroshi Iwasaki, Hideo Tsubouchi, Hung-Wen Li
Summary: In meiosis, Dmc1 and Rad51 are responsible for pairing and exchanging strands of homologous chromosomes. The mechanisms by which Swi5-Sfr1 and Hop2-Mnd1 stimulate Dmc1-driven recombination are still unclear. Through smFRET and TPM experiments, it was found that both Hop2-Mnd1 and Swi5-Sfr1 individually enhance Dmc1 filament assembly on ssDNA, and when added together, they provide further stimulation. The binding rate of Dmc1 is enhanced by Hop2-Mnd1 while the dissociation rate is specifically reduced by Swi5-Sfr1 during nucleation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Organic
Alexander Pontarelli, Christopher J. Wilds
Summary: This study describes the synthesis of C5-propynyl-2'-fluoroarabinonucleic acids (FANAP) and reveals that these modifications enhance RNA binding and support RNase H mediated cleavage. These findings suggest that C5-propynyl ANA/FANA modifications have promising potential for the design of therapeutic ONs.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Physical
Tzu-Yu Lee, Yi-Ching Li, Min-Guan Lin, Chwan-Deng Hsiao, Hung-Wen Li
Summary: DNA damage can lead to stalled or collapsed replication forks, which must be re-initiated by replication restart primosomes in order for bacterial survival. PriA specifically recognizes DNA fork structures and recruits other primosomal proteins, playing a crucial role in restart replication forks for proper DNA repair. Using single-molecule fluorescence colocalization experiment, the thermodynamic and real-time kinetic properties of fluorescence-labeled Gram-positive bacteria Geobacillus stearothermophilus PriA binding on DNA forks were measured, showing that PriA binds preferentially to a DNA fork structure with a fully duplexed leading strand at sub-nanomolar affinity.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)