Article
Multidisciplinary Sciences
Tobias Benkel, Mirjam Zimmermann, Julian Zeiner, Sergi Bravo, Nicole Merten, Victor Jun Yu Lim, Edda Sofie Fabienne Matthees, Julia Drube, Elke Miess-Tanneberg, Daniela Malan, Martyna Szpakowska, Stefania Monteleone, Jak Grimes, Zsombor Koszegi, Yann Lanoiselee, Shannon O'Brien, Nikoleta Pavlaki, Nadine Dobberstein, Asuka Inoue, Viacheslav Nikolaev, Davide Calebiro, Andy Chevigne, Philipp Sasse, Stefan Schulz, Carsten Hoffmann, Peter Kolb, Maria Waldhoer, Katharina Simon, Jesus Gomeza, Evi Kostenis
Summary: This study provides an alternative mechanism for carvedilol's cellular signaling, demonstrating that G proteins drive all detectable signals through beta(2)-adrenoceptors.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Jianfang Chen, Jiangting Liu, Yuan Yuan, Xin Chen, Fuhui Zhang, Xuemei Pu
Summary: This study explores the molecular mechanisms of biased activation induced by structural differences between different agonists. It reveals that G-protein-biased agonists and fi-arrestin-biased agonists achieve biased signaling through different conformational changes. In addition, the study also identifies specific conformations of ICL3 under specific agonists and the roles of key residues. These findings contribute to a better understanding of biased activation mechanisms and provide guidance for the design of biased drugs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Midhun K. Madhu, Annesha Debroy, Rajesh K. Murarka
Summary: This study investigates the conformational changes induced by phosphorylation in the beta 2-adrenergic receptor. Through molecular dynamics simulations, the researchers discover a new conformational state that is more favorable for binding beta-arrestin. The phosphorylated C-tail interacts with the cytosolic surface of the receptor, relaying the allosteric signal through correlated motions of residues. Atomistic insight into this phosphorylation-induced conformation is important for therapeutic drug design.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Review
Chemistry, Multidisciplinary
Lukasz Nierzwicki, Pablo Ricardo Arantes, Aakash Saha, Giulia Palermo
Summary: The study utilized molecular dynamics simulations to uncover the allosteric communication mechanism within CRISPR-Cas9, which is crucial for developing novel variants with improved genome editing capabilities.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2021)
Review
Genetics & Heredity
Xiangyan Shi, Ziwei Zhai, Yinglu Chen, Jindi Li, Lars Nordenskiold
Summary: This review summarizes recent advances in the study of chromatin dynamics and their regulatory factors, focusing on the conformational and dynamic properties of nucleosomes and nucleosome-protein complexes, and their implications for functional response and relevance.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Jianzhong Chen, Jian Wang, Qingkai Zeng, Wei Wang, Haibo Sun, Benzheng Wei
Summary: This study investigates the deactivation mechanism of the active β(2)AR receptor using Gaussian accelerated molecular dynamics simulations. The results show that the Gs protein is essential for stabilizing the active state of the receptor, and the motion of TM6 and TM5, as well as changes in the interaction networks between TM3, TM5, and TM6, drive the transition from the active to inactive state of the receptor.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Food Science & Technology
K. Kevion Darmawan, C. Tom Karagiannis, G. Jeff Hughes, M. Darryl Small, Andrew Hung
Summary: The study shows that acidic pH weakens interactions between lactoferrin and other proteins, but some contacts are maintained. This property could be used for developing novel food materials and indicates the potential antibacterial capability of apo-lactoferrin.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2021)
Article
Biology
Andrea Catte, Akash Deep Biswas, Giordano Mancini, Vincenzo Barone
Summary: This study investigates the protein-ligand interactions between L-DOPA, Droxidopa and β(2)-adrenergic receptor using molecular docking calculations, quantum mechanical calculations and molecular dynamics simulations. The results show that both ligands have similar binding anchor sites with adrenaline and comparable binding affinities.
Article
Biochemistry & Molecular Biology
Tetiana Serdiuk, Moutusi Manna, Cheng Zhang, Stefania A. Mari, Waldemar Kulig, Kristyna Pluhackova, Brian K. Kobilka, Ilpo Vattulainen, Daniel J. Muller
Summary: Cholesterol interacts with G protein-coupled receptors in cell membranes, modulating their assembly, stability, and conformation. This study shows that the cholesterol analog CHS can nonlinearly stabilize different structural regions of GPCRs and affect their functionality, with the strongest effects observed at physiological temperature.
Article
Biochemistry & Molecular Biology
Renjie Li, Zhuangwei Zhang, Jin Chen, Huihui Li, Hongjin Tang
Summary: In this study, new zein-gum arabic-tea polyphenols ternary complex nanoparticles were successfully prepared to encapsulate luteolin. These nanoparticles showed smaller particle size, higher encapsulation ability, and improved stability and retention rate of luteolin. They also exhibited stronger antioxidant activity and better sustainable release capacity under simulated gastrointestinal conditions.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Microbiology
Luz Maria Rodeles, Miguel Hernan Vicco, Alvaro Siano, Leonardo Andres Fuchs, Luz Maria Peverengo, Silvia Sanchez Puch, Cora Beatriz Cymeryng, Ivan Sergio Marcipar, Pablo Arias
Summary: This study investigated the prevalence of anti-beta 2 adrenergic receptor antibodies in patients with chronic Chagas disease (CCD) and their association with insulin resistance and atherogenic dyslipidemia. The findings suggest that these antibodies may contribute to metabolic disturbances and increase cardiovascular risk in CCD patients.
Article
Biochemistry & Molecular Biology
Gennady M. Verkhivker, Steve Agajanian, Deniz Oztas, Grace Gupta
Summary: In this study, an integrative computational approach was used to explore molecular mechanisms underlying the functional effects of the D614G mutation in SARSCoV-2 spike proteins. The findings suggest that the mutation enhances long-range signaling, stability, and thermodynamic preferences, promoting an increased number of stable communities and allosteric hub centers. This study provides insights into allosteric communications in the spike proteins, indicating that the D614G mutation affects stability and communication in residue interaction networks.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Multidisciplinary
Michael P. O'Hagan, Susanta Haldar, Juan C. Morales, Adrian J. Mulholland, M. Carmen Galan
Summary: Ligands with the capability to bind specifically to G-quadruplexes (G4s) and control their structure offer potential in developing novel therapies, technologies, and materials. Predictive tools are needed to drive ligand design, while molecular dynamics simulations provide insights into ligand binding mechanisms and perturbation of G4 structures. Experimental validation shows good agreement with simulated results, indicating the potential of metadynamics simulations in aiding the development of molecules influencing G4 structure.
Article
Biochemistry & Molecular Biology
Francis A. Acquah, Matthew Paramel, Adama Kuta, Syed R. Hussaini, David R. Wallace, Blaine H. M. Mooers
Summary: Research has shown that Indolizidine (-)-237D has potential efficacy in targeting nicotine addiction-related alpha 6 beta 2* nAChR, with nine distinct analogs identified through screening and molecular dynamics simulations, which could serve as lead candidates for drug development in treating nicotine addiction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Keerthi Krishnan, Hao Tian, Peng Tao, Gennady M. Verkhivker
Summary: In this study, the dynamic and energetic details of conformational landscapes and allosteric interactions in the ABL kinase domain that determine the kinase functions are examined using multiscale simulation approaches and dynamic network methods. The results elucidate how conformational transitions between active and inactive states employ allosteric switches to regulate intramolecular communication networks. The study provides a comprehensive computational analysis of long-range communications in the ABL kinase domain and identifies conserved regulatory hotspots that modulate kinase activity and allosteric crosstalk.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Susanta Haldar, Yashu Zhang, Ying Xia, Barira Islam, Sisi Liu, Francesco L. Gervasio, Adrian J. Mulholland, Zoe A. E. Waller, Dengguo Wei, Shozeb Haider
Summary: In this study, the mechanism of TMPyP4-induced RNA G-quadruplex (G4) unfolding was investigated using computational simulations and biophysical experiments. The results revealed that TMPyP4 interacts with RNA G4 through groove binding and top-face binding, disrupting hydrogen bonds between nucleotides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Sonia Di Gaetano, Luciano Pirone, Ioannis Galdadas, Serena Traboni, Alfonso Iadonisi, Emilia Pedone, Michele Saviano, Francesco Luigi Gervasio, Domenica Capasso
Summary: Galectins are soluble proteins involved in cancer progression and disease outcome, making them important targets for therapeutic intervention. Developing small inhibitors to selectively block galectin activity is a promising strategy for cancer therapy. This study designed a novel compound with high binding affinity to galectins and demonstrated its potential anticancer properties, paving the way for further development as an anticancer agent.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Christoph M. Schuesslbauer, Marcel Krug, Tobias Ullrich, Hannah M. Franklin, Steven Stevenson, Timothy Clark, Dirk M. Guldi
Summary: This study reports the photophysical characterization of empty-caged, tubular fullerenes D-5h-C-90 and D-5d-C-100 and compares their properties. It found that D-5d-C-100 has a larger optical band gap and luminesces at room temperature, while D-5h-C-90 does not luminesce. The study also discovered that D-5d-C-100 undergoes hole transfer with electron-donating triethylamines but not electron transfer with electron-accepting methyl viologens.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Medicinal
Dominykas Lukauskis, Marley L. Samways, Simone Aureli, Benjamin P. Cossins, Richard D. Taylor, Francesco Luigi Gervasio
Summary: Predicting the correct pose and binding affinity of a ligand to a protein is crucial in computer-aided drug discovery. OpenBPMD, an open-source Python reimplementation of BPMD, demonstrates performance matching or exceeding the original BPMD, and the combination with a grand-canonical Monte Carlo algorithm improves prediction accuracy.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Matthias Hennemann, Timothy Clark
Summary: A modified neglect of differential overlap theory was used to parameterize water and its oligomers, with the addition of polarization functions, Feynman dispersion, and a slight modification of hydrogen nucleus treatment. The results demonstrated the feasibility of obtaining accurate geometries and energies for hydrogen-bonded water aggregates.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biology
Alberto Borsatto, Obaeda Akkad, Ioannis Galdadas, Shumeng Ma, Shymaa Damfo, Shozeb Haider, Frank Kozielski, Carolina Estarellas, Francesco Luigi Gervasio
Summary: Non-structural protein 1 (Nsp1) of SARS-CoV-2 is a main pathogenicity factor that suppresses host gene expression and innate immune response. This study identifies druggable pockets in Nsp1 and confirms their potential as targets for designing inhibitors. Targeting these pockets could disrupt the Nsp1-mRNA complex and provide a novel avenue for developing inhibitors against other Nsp1s in related coronaviruses.
Article
Chemistry, Medicinal
Jacqueline C. Calderon, Passainte Ibrahim, Dorothea Gobbo, Francesco Luigi Gervasio, Timothy Clark
Summary: We propose a metadynamics protocol to characterize the activation free-energy profiles of G-protein coupled receptors, focusing on the 5HT1A-receptor as a proof-of-principle study. By using the A100 activation index based on inter-helix distances, we perform metadynamics simulations and obtain free-energy profiles for the receptor in various complexes. Our results not only agree with previous experimental and computational data, but also provide detailed insights into the differences between active and inactive conformations and the role of microswitches in the activation mechanism.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Henrik Gotfredsen, Dominik Thiel, Phillip M. Greibel, Lan Chen, Marcel Krug, Ilias Papadopoulos, Michael J. Ferguson, Mogens Brondsted Nielsen, Tomas Torres, Timothy Clark, Dirk M. Guldi, Rik R. Tykwinski
Summary: This study investigates the influence of sensitizer-chromophore geometry on the separation of singlet excited states into triplet excited states. Two conjugates with different arrangements were synthesized and compared. The results show that the energy transfer rate is 26 times faster in the peripheral arrangement, even though the chromophores are farther apart. This rate acceleration is attributed to the more favorable relative orientation of the transition dipole moments in the peripheral structure. These findings are of significant importance for solar energy research.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Arthur Radoux-Mergault, Lucie Oberhauser, Simone Aureli, Francesco Luigi Gervasio, Miriam Stoeber
Summary: Intracellular GPCRs, such as ORs, can be activated by permeant ligands in specific subcellular compartments, which has implications for agonist selectivity. This study examines the recruitment of signal transducers to mu-and delta-ORs in the Golgi apparatus and plasma membrane. The findings reveal differences in signaling effects and coupling selectivity between Golgi and plasma membrane ORs, suggesting that subcellular location plays a role in defining the effects of opioid drugs.
Article
Chemistry, Physical
Valerio Rizzi, Simone Aureli, Narjes Ansari, Francesco Luigi Gervasio
Summary: Enhanced sampling techniques, such as using collective variables (CVs) or parallel tempering, have greatly advanced molecular dynamics simulations for studying rare events and calculating free energy differences. We propose a replica exchange method called OneOPES that combines the advantages of multireplica simulations and CV-based enhanced sampling, providing an efficient and robust framework for complex systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Multidisciplinary
Yifan Bo, Yuxuan Hou, Dominik Thiel, Renee Weiss, Timothy Clark, Michael J. Ferguson, Rik R. Tykwinski, Dirk M. Guldi
Summary: This study designs two tetracene dimers with different linking modes, and characterizes the interplay between intramolecular singlet fission (intra-SF) and intramolecular triplet-triplet annihilation up-conversion (intra-TTA-UC) through steady-state and time-resolved absorption and fluorescence spectroscopy. By using Pd-phthalocyanine as a sensitizer, intra-TTA-UC is achieved in the two dimers via indirect photoexcitation in the near-infrared part of the solar spectrum. Temperature-dependent measurements reveal the impact of thermal effects on intra-SF and intra-TTA-UC in different dimers.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Jacqueline C. Calderon, Alberto Herrera, Frank W. Heinemann, Jens Langer, Anthony Linden, Ahmed Chelouan, Alexander Grasruck, Rafael Anez, Timothy Clark, Romano Dorta
Summary: The inversion barriers Delta G double dagger for planar chiral phosphine-alkene and sulfonamide-alkene hybrid ligands based on phenyl-dibenz-[b,f]-azepine have been determined by density-functional theory calculations. Analysis of the structural and electronic characteristics of the minima and transition states explains the magnitudes of Delta G double dagger and the geometrical changes during the inversion process. The steric repulsion caused by bulky substituents attached to the azepine nitrogen atom has a pronounced effect on the Delta G double dagger value, explaining the stereochemical stability of the ligands.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Wiebke Zika, Andreas Hirsch, Rene Weiss, Simone Pinter, Christoph M. Schuesslbauer, Timothy Clark, Andreas Hirsch, Dirk M. Guldi
Summary: This study investigates the interconversion between QC and NBD and their application in energy storage through photo-assays. An oxidative electron transfer is observed during the QC-to-NBD isomerization using transient absorption spectroscopy. The complementary use of time-resolved and steady-state spectroscopies allows for a complete description of the photoisomerization reaction of NBDs.
Article
Chemistry, Multidisciplinary
Susanta Haldar, Yashu Zhang, Ying Xia, Barira Islam, Sisi Liu, Francesco L. Gervasio, Adrian J. Mulholland, Zoe A. E. Waller, Dengguo Wei, Shozeb Haider
Summary: The cationic porphyrin TMPyP4 can stabilize different topologies of DNA G4 structures via multiple binding modes, but can have both stabilizing and destabilizing effects on RNA G4 structures. The mechanism of TMPyP4-induced RNA G4 unfolding involves a two-state interaction mechanism with groove-bound and top-face-bound conformations. TMPyP4 disrupts Hoogsteen H-bonds between guanine bases and intercalates between the top-to-bottom G-tetrads, revealing a strong correlation between computational and experimental approaches.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Alexander M. Prophet, Kritanjan Polley, Gary J. Van Berkel, David T. Limmer, Kevin R. Wilson
Summary: The oxidation kinetics of iodide by ozone at the air-water interface is studied in single microdroplets. Molecular simulations and kinetic modeling are used to understand the underlying multiphase mechanism.
Article
Chemistry, Multidisciplinary
Rong Zhang, Jiajing Lan, Fei Wang, Shumei Chen, Jian Zhang
Summary: By utilizing 1,1'-ferrocene dicarboxylic acid as a chelating and surface protection ligand, we have synthesized multi-nuclear indium oxide clusters with varying nuclear sizes, including heptanuclear and thirteen-nuclear clusters. These clusters possess labile coordination sites, allowing for structural modification and self-assembly, resulting in the formation of various cluster structures.
Article
Chemistry, Multidisciplinary
Hui Wang, Hui Liu, Mingsen Wang, Jiaheng Hou, Yongjun Li, Yuancheng Wang, Yingjie Zhao
Summary: Two supramolecular complexes were prepared using CBs and M1, and their single-crystal structures were analyzed by SCXRD. The unexpected 1:2 self-assembly structure between M1 and CB[8] was discovered for the first time. These complexes exhibit unique photophysical properties and provide valuable information about the structure and photophysical properties of supramolecular complexes.
Article
Chemistry, Multidisciplinary
Chang-Hee Lee, Sookil Park, Sanggil Kim, Ji Young Hyun, Hyun Soo Lee, Injae Shin
Summary: The epidermal growth factor receptor (EGFR) is a cell-surface glycoprotein involved in cell proliferation and tumor development. This study used a fluorescently labeled EGFR to investigate its time-dependent endocytosis in live cells and found that appended glycans affect EGFR internalization. Additionally, the study detected sialic acid residues attached to EGFR on the live cell surface using FRET-based imaging. This research provides valuable insights into the cellular functions of EGFR.
Article
Chemistry, Multidisciplinary
Subhankar Sahu, Lokesh Kumar, Sumita Das, Dipti Gupta, Ruchi Anand
Summary: This study proposes a strategy that combines organic electronics with biosensor scaffolds to create a compact device for monitoring environmental aromatic pollution. By coupling biosensing protein MopR with an organic electrochemical transistor (OECT), a sensor module capable of efficient detection of phenol was designed. Exclusive phenol detection with minimal loss of sensitivity could be achieved in complex pollutant mixtures and real environmental samples.
Review
Chemistry, Multidisciplinary
Changseok Lee, Hyung-Joon Kang, Sungwoo Hong
Summary: The formation of C-N bonds through hydroamination reactions catalyzed by nickel hydrides has been a topic of recent interest. This approach offers a way to efficiently transform a variety of alkene and alkyne substrates into compounds enriched with C-N bonds. The review provides a concise overview of the underlying reaction mechanisms and aims to stimulate further progress in NiH-catalytic techniques and catalyst design.
Article
Chemistry, Multidisciplinary
Yueci Wu, Lu-Lu Sun, Hai-Hao Han, Xiao-Peng He, Weiguo Cao, Tony D. James
Summary: Drug-induced liver injury (DILI) is a common cause of acute liver failure in the USA and Europe, but most cases can be recovered or prevented by discontinuing the offending drug. Recent research has found that peroxynitrite (ONOO-) can be used as a potential indicator for early diagnosis of DILI, and there is an urgent need to establish a method to detect and track peroxynitrite in DILI cases. In this study, a FRET-based nano fluorescent probe CD-N-I was developed, which showed high selectivity and sensitivity in detecting peroxynitrite. The probe successfully detected exogenous peroxynitrite in live cells and endogenous peroxynitrite in APAP-induced liver injury of HepG2 cells.
Article
Chemistry, Multidisciplinary
Dmitry L. Lipilin, Mikhail O. Zubkov, Mikhail D. Kosobokov, Alexander D. Dilman
Summary: This article describes a direct photocatalytic method for the thiolation of unprotected acids, which was previously challenging. By using a thionocarbonate reagent with an N-O bond, the efficient conversion of carboxylic acids to thiols is achieved.
Article
Chemistry, Multidisciplinary
Jason Malenfant, Lucille Kuster, Yohann Gagne, Kouassi Signo, Maxime Denis, Sylvain Canesi, Mathieu Frenette
Summary: Raman microscopy can reveal compound-specific vibrational fingerprints without sample preparation. The combination of efficient theoretical calculations and a user-friendly software can accurately predict peak positions and provide match scores to assist with structure determination.
Article
Chemistry, Multidisciplinary
Jayoh A. Hernandez, Paul S. Micus, Sean Alec Lois Sunga, Luca Mazzei, Stefano Ciurli, Gabriele Meloni
Summary: Essential trace metals play crucial roles in the survival and virulence of bacterial pathogens. Helicobacter pylori requires nickel for colonization and persistence in the stomach, and NixA is an essential nickel transporter in this process. This study characterizes the selectivity and electrogenic nature of NixA-mediated nickel transport.
Article
Chemistry, Multidisciplinary
Tarali Devi, Kuheli Dutta, Jennifer Deutscher, Stefan Mebs, Uwe Kuhlmann, Michael Haumann, Beatrice Cula, Holger Dau, Peter Hildebrandt, Kallol Ray
Summary: This study emphasizes the importance of subtle electronic changes and secondary interactions in the stability of biologically relevant metal-dioxygen intermediates. It also shows that the role of the chloride ligand in stabilizing the Fe-III-(OOBu)-Bu-t moiety can extend to other anions, including the thiolate ligand.
Article
Chemistry, Multidisciplinary
Jacqueline R. Santhouse, Jeremy M. G. Leung, Lillian T. Chong, W. Seth Horne
Summary: By studying the folding kinetics and mechanism of the BdpA sequence, researchers found that altering the backbone connectivity can affect protein folding. This suggests that protein mimetic chains have a significant degree of plasticity in transitioning between unfolded and folded states.
Article
Chemistry, Multidisciplinary
Divanshu Gupta, Ralf Einholz, Holger F. Bettinger
Summary: This study presents the first direct spectroscopic evidence of a cyclic seven-membered iminoborane. Compared to linear amino-iminoboranes, this cyclic iminoborane exhibits weakened bond strength and lower Lewis acidity value. The study suggests that the reduced ring strain of cyclic iminoborane prevents nitrogen fixation but allows facile (2 + 2) cycloaddition reaction with C2H4.
Article
Chemistry, Multidisciplinary
Renny Mathew, Aniruddha Mazumder, Praveen Kumar, Julie Matula, Sharmarke Mohamed, Petr Brazda, Mahesh Hariharan, Brijith Thomas
Summary: This study reveals the packing arrangement of partially disordered nitro-perylenediimide (NO2-PDI) using a synergistic approach that combines 3D ED, ssNMR, and DFT techniques. By overcoming these challenges, this methodology opens up new avenues for material characterization, driving exciting advancements in the field.