Article
Multidisciplinary Sciences
Ilya A. Vakser, Sergei Grudinin, Nathan W. Jenkins, Petras J. Kundrotas, Eric J. Deeds
Summary: Computational methodologies are being used to model the entire cell at the molecular level. This study combines protein docking and molecular simulations to develop an approach that can simulate cellular processes at unprecedented timescales and all-atom resolution. The approach successfully captures the dynamics of protein interactions and has been validated across various protein systems.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Matthew Biancalana, Eviatar Natan, Michael J. Lenardo, Alan R. Fersht
Summary: The study reveals that the p50 and p65 Rel subunits in the NF-kappa B complex exhibit different kinetic stability, with a strong preference for the formation of the p50/p65 heterodimer over homodimers. This suggests that cells can modulate NF-kappa B activity by fine-tuning the relative proportions of p50 and p65 proteins and their expression time.
Article
Chemistry, Analytical
Daniele Peterle, Thomas E. Wales, John R. Engen
Summary: During HDX-MS analysis, understanding back-exchange is crucial for correction and calculation purposes. This study presents a fast and effective protocol for preparing maxD control samples, utilizing denaturation and deuteration to achieve optimal levels of deuteration within a short timeframe. The results show that this protocol performs equivalently to previous methods, but with significantly reduced time and effort.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Julia Kotschy, Benedikt Soeldner, Himanshu Singh, Suresh K. Vasa, Rasmus Linser
Summary: This study reports the experimental identification of internal microsecond-scale dynamics of a high-affinity ligand tightly bound to the enzyme human carbonic anhydrase II (hCAII), even within a crystalline lattice. The authors demonstrate the existence of ligand's rotamer jumps through both solution and solid-state NMR experiments, and gain further insights through molecular dynamics simulations. This experimental confirmation of rotameric jumps in bound ligands within proteins in solution or the crystalline state is significant for understanding host-guest interactions in biology and supra-molecular chemistry, and for facilitating medicinal chemistry in drug research.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Jia-Ahn Pan, Justin C. Ondry, Dmitri Talapin
Summary: A direct photopatterning approach for lead halide perovskite nanocrystals has been introduced, allowing for the creation of patterns through molecular cleavage after photoirradiation. Postpatterning ligand exchange results in increased photoluminescence quantum yields and emission wavelength tunability. The patterned nanocrystal films exhibit photoconductive behavior, indicating good electrical contact between the nanocrystals.
Article
Chemistry, Physical
Yoshihiro Matsumura, Shinji Saito
Summary: This study investigates the microscopic aspects of dynamic disorder in a protein's isomerization dynamics, shedding light on the transition from slow modulation to fast modulation. Through theoretical modeling and analysis, the research uncovers the microscopic origins of dynamic disorder in complex molecular processes.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Chemistry, Analytical
Jason M. Hogan, Peter S. Lee, Susan C. Wong, Sean M. West, Winse H. Morishige, Christine Bee, Gamze Camdere Tapia, Arvind Rajpal, Pavel Strop, Gavin Dollinger
Summary: This article presents a novel application of mass spectrometry-based carbene chemical footprinting for identification of antibody binding epitopes. The technique allows for high-resolution mapping of epitopes at the single-residue level and has been validated using X-ray crystallography and yeast surface display epitope mapping. The characterized epitopes provide important information for understanding competitive binding results and accelerating the drug discovery process.
ANALYTICAL CHEMISTRY
(2023)
Article
Materials Science, Multidisciplinary
Yang Liu, Muyu Liu, Hua Li, Guitao Luo, Hongbo Tan, Qimin Liu
Summary: This study proposed a theoretical model to investigate multi-mineral reactive transport processes and the effect of multi-mineral reactions on cement hydration kinetics shifting from silicate to aluminate dominance. The model calculates the reaction rates, ionic diffusion, and adsorption based on the ionic concentration, and the hydration heat flow based on the reaction rates. The model was validated and used to study the combined effect of multi-mineral reactions on hydration kinetics.
MATERIALS & DESIGN
(2023)
Article
Chemistry, Multidisciplinary
Orian Elimelech, Meirav Oded, Daniel Harries, Uri Banin
Summary: Binary compositions of surface ligands significantly improve the colloidal stability and fluorescence quantum yield of nanocrystals (NCs). In this study, the thermodynamics of a ligand exchange reaction of CdSe NCs with alkylthiol mixtures were investigated using isothermal titration calorimetry (ITC). It was found that the interligand interactions determine the clustering patterns of the ligand shell structure. This work provides fundamental insights for the design of smart surfaces in NC-based applications.
Article
Multidisciplinary Sciences
Yuki Toyama, Robert W. Harkness, Lewis E. Kay
Summary: This study investigates the interaction between HtrA2 and protein substrates using NMR spectroscopy and finds that HtrA2 binds to substrates through two parts, and multivalent binding significantly stimulates its catalytic activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Inorganic & Nuclear
Yaru Zhen, Shan Jin, Xi Kang, Chang Xu, Cao Fang, Daqiao Hu, Manzhou Zhu
Summary: This study reports on a phosphine ligand induced intercluster transformation process and investigates its structure and photochemical properties. The findings are of significant importance for the customized applications of metal nanoclusters.
INORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Automation & Control Systems
Karolina Tran, Han Wang, Meike Pieters, Maria Antonietta Loi
Summary: This article presents the first example of synaptic transistors utilizing colloidal quantum dots (CQDs) as active material. It is demonstrated that PbS-CQDs with metal halide and perovskite-like ligands are ideal for synaptic transistors, exhibiting both short- and long-term plasticity. Interestingly, by changing the chemistry of the quantum dot outer monolayer, a drastic change in the temporal response of learning is observed, demonstrating the possibility of engineering materials with learning at multiple timescales, similar to biological synapses.
ADVANCED INTELLIGENT SYSTEMS
(2023)
Article
Polymer Science
Sarah C. Seeger, Kevin D. Dorfman, Timothy P. Lodge
Summary: The combination of umbrella sampling and dissipative particle dynamics simulations reveals that the core block A of the expelled chain remains partially stretched at the transition state. The free energy barrier linearly increases with the Flory-Huggins interaction parameter chi, and the spherical core structure deforms near the transition state at large interaction energies.
Article
Multidisciplinary Sciences
Seok Jeong, Junmo Seong, Sung Wook Moon, Jaewoong Lim, Seung Bin Baek, Seung Kyu Min, Myoung Soo Lah
Summary: The spatial distribution of mixed building blocks in metal-organic frameworks can be modulated by tuning the reaction temperature, leading to the formation of core-shell and uniform microstructures.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Hossein Lanjanian, Shadi Hosseini, Zahra Narimani, Sogol Meknatkhah, Gholam Hossein Riazi
Summary: The study aimed to develop a pipeline to identify potential protein-protein interaction inhibitors by screening phytochemicals from Middle Eastern antiviral herbs. A series of simulations were performed to determine candidate molecules for inhibiting PPIs involved in COVID-19.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Saeko Yanaka, Shigetaka Nishiguchi, Rina Yogo, Hiroki Watanabe, Jiana Shen, Hirokazu Yagi, Takayuki Uchihashi, Koichi Kato
Summary: This study employed high-speed atomic force microscopy to quantitatively visualize the interaction between mouse IgG and the C1 complex. The results showed that C1q is restricted in terms of internal motion and has a stronger binding affinity for IgG2b assemblages. Additionally, a 1:1 stoichiometric interaction between C1/C1q and an IgG2a variant was observed in the absence of an antigen.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Saeko Yanaka, Hirokazu Yagi, Rina Yogo, Masayoshi Onitsuka, Koichi Kato
Summary: Mammalian cells are commonly used for producing recombinant glycoproteins, but the high production costs are a drawback. We developed a cost-saving method by culturing the cells under glutamine-free conditions for uniform isotope labeling.
JOURNAL OF BIOMOLECULAR NMR
(2022)
Article
Chemistry, Multidisciplinary
Yutaka Mahana, Izuru Ohki, Erik Walinda, Daichi Morimoto, Kenji Sugase, Masahiro Shirakawa
Summary: This study determined the structure of the MBD domain of the MBD6 protein in Arabidopsis thaliana and investigated its binding properties to methylated DNA. The binding affinity of the MBD domain for methyl-CpG-containing DNA was found to be lower than that of mammalian MBD domains, due to the absence of positively charged residues. This research provides insights into how MBD proteins mediate epigenetic signals in plant cells.
Article
Hematology
Atsushi Tanaka, Taizo A. Nakano, Masaki Nomura, Hiromi Yamazaki, Jan P. Bewersdorf, Roger Mulet-Lazaro, Simon Hogg, Bo Liu, Alex Penson, Akihiko Yokoyama, Weijia Zang, Marije Havermans, Miho Koizumi, Yasutaka Hayashi, Hana Cho, Akinori Kanai, Stanley C. Lee, Muran Xiao, Yui Koike, Yifan Zhang, Miki Fukumoto, Yumi Aoyama, Tsuyoshi Konuma, Hiroyoshi Kunimoto, Toshiya Inaba, Hideaki Nakajima, Hiroaki Honda, Hiroshi Kawamoto, Ruud Delwel, Omar Abdel-Wahab, Daichi Inoue
Summary: This study identifies a novel oncogenic RNA-splicing derived isoform of EVI1 that is frequently present in inv(3)/t(3;3) acute myeloid leukemia. It is generated by mutations in the core RNA splicing factor SF3B1, which is commonly cooccurring with inv(3)/t(3;3) genomic alteration. The mutant SF3B1 spliceosome promotes mis-splicing of EVI1 and enhances self-renewal of hematopoietic stem cells, contributing to leukemic transformation.
Review
Biochemistry & Molecular Biology
Koichi Kato, Hirokazu Yagi, Saeko Yanaka
Summary: The three-dimensional structures of glycans in aqueous solutions are in constant fluctuation and play a crucial role in the interactions with sugar-recognizing molecules and the regulation of sugar-bearing protein functions. Understanding the conformational dynamics of both bound and unbound glycans is essential in glycotechnology and drug discovery targeting glycan recognition systems. Additionally, the glycans in glycoproteins also influence the conformational dynamics of the protein part, highlighting the importance of considering the intramolecular interaction network between the glycans and the protein in molecular design. Experimental, computational, and information science approaches will be increasingly important in deciphering the biological information carried by the four-dimensional structures of glycans.
TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Keiichi Hata, Naohiro Kobayashi, Keita Sugimura, Weihua Qin, Deis Haxholli, Yoshie Chiba, Sae Yoshimi, Gosuke Hayashi, Hiroki Onoda, Takahisa Ikegami, Christopher B. Mulholland, Atsuya Nishiyama, Makoto Nakanishi, Heinrich Leonhardt, Tsuyoshi Konuma, Kyohei Arita
Summary: This study determined the structure of the mouse UHRF1 plant homeodomain (PHD) complexed with DPPA3 using nuclear magnetic resonance. The results showed that DPPA3 induces alpha-helices upon binding to UHRF1 PHD, leading to stable complex formation through multifaceted interactions. Mutations in the binding interface and unfolding of the DPPA3 helical structure inhibit the binding of UHRF1 and its chromatin localization.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Saeko Yanaka, Maho Yagi-Utsumi, Koichi Kato, Kunihiro Kuwajima
Summary: The residual structures in unfolded proteins were studied, and it was found that NH protons under alpha-helical hydrogen bond were significantly protected, indicating the formation of stronger hydrogen bonds under native folding conditions. The results are helpful in deducing the structure of early folding intermediates.
Article
Immunology
Saeko Yanaka, Rina Yogo, Hirokazu Yagi, Masayoshi Onitsuka, Natsumi Wakaizumi, Yuki Yamaguchi, Susumu Uchiyama, Koichi Kato
Summary: Although the interactions of small molecular drugs with serum proteins have been extensively studied, little is known about the effects of serum components on therapeutic antibody functions. This study reveals that human serum albumin (HSA) and the Fab fragment from the pooled serum polyclonal IgG compromise the antibody-dependent cellular cytotoxicity (ADCC) mediated by rituximab and Fc gamma receptor III (Fc gamma RIII). Our nuclear magnetic resonance data provide direct evidence for the interactions between HSA and rituximab's Fab and Fc regions, as well as Fc gamma RIII (sFc gamma RIII). These findings highlight the importance of considering serum-protein interactions in the design and application of antibody-based drugs.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Methanee Hiranyakorn, Maho Yagi-Utsumi, Saeko Yanaka, Naoya Ohtsuka, Norie Momiyama, Tadashi Satoh, Koichi Kato
Summary: We characterized the dynamic conformational interconversions of Lys48-linked ubiquitin chains, which involve both intermolecular and intramolecular interactions. The hydrophobic Ub-Ub interaction in diUb was reinforced by cysteine substitution of Lys48 of the distal Ub unit. Additionally, the mutational modification impacted the exposure of the most distal Ub unit in triUb.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Eri Imagawa, Latisha Moreta, Vinod K. Misra, Claire Newman, Tsuyoshi Konuma, Kimihiko Oishi
Summary: A mild phenotype including cleft palate, hypotonia, developmental delay, and minor dysmorphisms was observed in a 3-year-old male with a missense RBM10 variant. The variant affected the expression of downstream genes NUMB and TNRC6A through alternative splicing regulation, resulting in non-lethal developmental delays.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Nan Liu, Tsuyoshi Konuma, Rajal Sharma, Deyu Wang, Nan Zhao, Lingling Cao, Ying Ju, Di Liu, Shuai Wang, Almudena Bosch, Yifei Sun, Siwei Zhang, Donglei Ji, Satoru Nagatoishi, Noa Suzuki, Masaki Kikuchi, Masatoshi Wakamori, Chengcheng Zhao, Chunyan Ren, Thomas Jiachi Zhou, Yaoyao Xu, Jamel Meslamani, Shibo Fu, Takashi Umehara, Kouhei Tsumoto, Satoko Akashi, Lei Zeng, Robert G. Roeder, Martin J. Walsh, Qiang Zhang, Ming-Ming Zhou
Summary: Histone lysine acylation, such as acetylation and crotonylation, plays a crucial role in gene transcription, but our understanding has been limited to transcriptional activation. This study reveals that histone H3 lysine 27 crotonylation (H3K27cr) is involved in gene transcriptional repression. The YEATS domain of GAS41 selectively recognizes H3K27cr in chromatin and forms a complex with SIN3A-HDAC1 co-repressors. The proto-oncogenic transcription factor MYC recruits the GAS41/SIN3A-HDAC1 complex to repress genes, including the cell-cycle inhibitor p21.
Article
Biochemical Research Methods
Tsuyoshi Konuma, Jun-ichi Kurita, Takahisa Ikegami
Summary: The relaxation dispersion (rd) of nuclear magnetic resonance provides thermodynamic and kinetic information for molecules with exchanging conformations. We developed a new pulse sequence (AFTAC) that can suppress artifacts in magnetization components and demonstrated its effectiveness in measuring methyl groups. The AFTAC method achieves similar artifact suppression quality in SI, SI2, and SI3 spin systems.
JOURNAL OF MAGNETIC RESONANCE
(2023)
Article
Chemistry, Physical
Yusuke Shuto, Erik Walinda, Daichi Morimoto, Kenji Sugase
Summary: Weak electric fields disrupt the local structure of proteins and induce rotational mobility of hydration water. The alignment tendency of bulk water with electric fields is stronger than that of hydration water. The findings emphasize the importance of local dipoles and their electric polarizability in net-uncharged biomolecules.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Biochemistry & Molecular Biology
Tomoki Sorada, Erik Walinda, Masahiro Shirakawa, Kenji Sugase, Daichi Morimoto
Summary: Cyclization increases the thermal stability of Lys48-linked diubiquitin and represses its interdomain motion. Coarse-grained molecular dynamics simulations reveal how cyclization slows down the open-closed domain motion of diubiquitin.
Article
Chemistry, Multidisciplinary
Ryu Hashimoto, Masafumi Minoshima, Souhei Sakata, Fumihito Ono, Hirokazu Ishii, Yuki Watakabe, Tomomi Nemoto, Saeko Yanaka, Koichi Kato, Kazuya Kikuchi
Summary: In this study, visible-light-sensitive protecting groups with high uncaging cross sections were developed for precise control of bioactivity. Two-photon photolysis reactions were achieved using near-infrared laser, and green-light illumination enabled optical control of biological functions.