Article
Virology
Weijun He, Weixu Zhang, Huixin Yan, Hefeng Xu, Yuan Xie, Qizhong Wu, Chengmin Wang, Guoying Dong
Summary: H1N1 influenza viruses have exhibited high resistance to adamantanes, with mutant variants mainly appearing in North America and Europe, becoming circulating strains worldwide since 2009. The study found that 80.65% of human H1N1 influenza viruses and 74.61% of swine H1N1 influenza viruses exhibited adamantanes resistance, while the frequency was only 1.86% in avian H1N1 influenza viruses.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Article
Chemistry, Physical
Lorena Ruano, Gustavo Cardenas, Juan J. Nogueira
Summary: This study investigates the intermolecular interactions between platinum-based anticancer drugs and lipid bilayers, finding that the permeation of cisplatin through a model membrane involves complex interactions with the polar and non-polar regions of the lipid bilayer, influenced by long-range electrostatic and hydrogen bond interactions. The permeation free-energy profile is determined by a balance between drug/lipid interactions, dehydration of the drug, and changes in membrane ordering along the permeation pathway.
Article
Biochemistry & Molecular Biology
Maksim A. Kalutsky, Timur R. Galimzyanov, Rodion J. Molotkovsky
Summary: This study investigates the fusion mechanism of monolayer and bilayer membranes during the interaction between lipid droplets and peroxisomes. Through energy trajectory and molecular dynamics simulation, it is found that the stalk formed during the fusion process is energetically more stable and has a lower energy barrier compared to bilayer fusion. The further evolution of the stalk is dependent on the spontaneous curvature of the membrane, possibly related to the incorporation of free fatty acids.
Article
Chemistry, Physical
Christopher Kang, Rui Sun
Summary: The research indicates that α-synuclein prefers binding to the outer leaflet of synaptic vesicles due to Coulombic interaction, and the association with the membrane facilitates protein folding.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biology
Stephanie Bolik, Alexander Schlaich, Tetiana Mukhina, Alberto Amato, Olivier Bastien, Emanuel Schneck, Bruno Deme, Juliette Jouhet
Summary: The study compared the properties of betaine lipids and phosphatidylcholine (PC) lipids through neutron diffraction experiments and dynamic molecular simulations. It found that betaine lipids are thicker and more rigid than PC lipids, and they have higher repulsive forces, possibly due to unscreened electrostatic contribution. Furthermore, betaine lipids can exist in both gel and fluid phases.
Article
Chemistry, Multidisciplinary
Rashad Kariuki, Rowan Penman, Saffron J. Bryant, Rebecca Orrell-Trigg, Nastaran Meftahi, Russell J. Crawford, Chris F. McConville, Gary Bryant, Kislon Voitchovsky, Charlotte E. Conn, Andrew J. Christofferson, Aaron Elbourne
Summary: Nanomaterials have the potential to revolutionize biological and biomedical research, and this study provides detailed insights into how gold nanoparticles interact with phospholipid membranes. The study shows that the nanoparticles can be absorbed and internalized by fluid-phase membranes, and partially embed into gel-phase membranes, causing perturbations throughout the bilayers.
Article
Chemistry, Physical
Weiyi Lin, Pingping Zhuang
Summary: This study investigates the charge distribution in bilayer graphene and reveals that the hole distribution in the top and bottom layers of AB-BLG and t-BLG are similar, with the additional layer reducing the charge exchange at the graphene/dopant interface.
APPLIED SURFACE SCIENCE
(2022)
Article
Food Science & Technology
Natalia Kuzmina, Pavel Volynsky, Ivan Boldyrev, Anna Alekseeva
Summary: Bee venom PLA2 exhibits two additional interface binding modes and enzyme activity through constant switching between different orientations. This switching has biological significance in terms of enzyme movement along the membrane, product release in a biological milieu, and enzyme desorption from the bilayer surface.
Article
Materials Science, Multidisciplinary
Tun Naw Sut, Bo Kyeong Yoon, Won-Yong Jeon, Joshua A. Jackman, Nam-Joon Cho
Summary: Supported lipid bilayer (SLB) coatings, versatile cell-membrane-mimicking biointerfaces, have been expanded for medical and biotechnology applications, facilitating various studies and applications like biosensors, diagnostics, and antifouling surfaces.
APPLIED MATERIALS TODAY
(2021)
Article
Physics, Multidisciplinary
Lukas Sponfeldner, Nadine Leisgang, Shivangi Shree, Ioannis Paradisanos, Kenji Watanabe, Takashi Taniguchi, Cedric Robert, Delphine Lagarde, Andrea Balocchi, Xavier Marie, Iann C. Gerber, Bernhard Urbaszek, Richard J. Warburton
Summary: The coupling of intralayer A and B excitons and interlayer excitons (IE) in a two-dimensional semiconductor, homobilayer MoS2, is studied. The optical susceptibility measurements reveal both the magnitude and phase of the coupling constants. The coupling mechanisms between IE-B and IE-A are interpreted as hole tunneling and electron-hole exchange, respectively. It is also found that even in a monolayer, the A and B excitons have mixed spin states. Moreover, a bright and highly tunable lowest-energy momentum-direct exciton is achieved under high electric fields.
PHYSICAL REVIEW LETTERS
(2022)
Article
Nanoscience & Nanotechnology
Namphung Peimyoo, Thorsten Deilmann, Freddie Withers, Janire Escolar, Darren Nutting, Takashi Taniguchi, Kenji Watanabe, Alireza Taghizadeh, Monica Felicia Craciun, Kristian Sommer Thygesen, Saverio Russo
Summary: Interlayer excitons in bilayer MoS2 can be electrically controlled at room temperature, offering new opportunities for excitonic devices. The large oscillator strength of the IL excitonic states is preserved as their energies are manipulated by the electric field, indicating potential for practical applications.
NATURE NANOTECHNOLOGY
(2021)
Article
Engineering, Chemical
Keita Yano, Masayuki Iwamoto, Takaaki Koshiji, Shigetoshi Oiki
Summary: This study establishes an accurate method for evaluating the osmotic permeability of lipid bilayers under constant tension, and known unstirred layers. This method helps to better understand the water flux process across cell membranes by quantifying membrane tension and unstirred layers.
JOURNAL OF MEMBRANE SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Maria C. Oliveira, Maksudbek Yusupov, Annemie Bogaerts, Rodrigo M. Cordeiro
Summary: This study investigates the distribution of lipid aldehydes (LAs) in phase-separated membranes (PSMs) and finds that LAs derived from mono-unsaturated lipids accumulate at the interface between liquid-ordered/liquid-disordered domains, while LAs derived from poly-unsaturated lipids remain in the liquid-disordered domain. These findings are important for understanding the effects of oxidized lipids on membrane structure, properties, and organization.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Multidisciplinary Sciences
Fabian C. Herbert, Sameera S. Abeyrathna, Nisansala S. Abeyrathna, Yalini H. Wijesundara, Olivia R. Brohlin, Francesco Carraro, Heinz Amenitsch, Paolo Falcaro, Michael A. Luzuriaga, Alejandra Durand-Silva, Shashini D. Diwakara, Ronald A. Smaldone, Gabriele Meloni, Jeremiah J. Gassensmith
Summary: This study demonstrates the successful generation and immobilization of metastable lipid, protein-detergent, and protein-lipid supramolecular complexes within a zeolitic-imidazole framework (ZIF) to enhance stability against various stressors. The immobilized complexes exhibit resistance to elevated temperatures, chemical denaturants, aging, and mechanical stresses, maintaining their native morphology, structure, and activity. Immobilizing lipid nanoparticles and lipid-protein assemblies remains challenging due to lipid dynamics and protein instability, but this work shows promise for long-term storage at room temperature.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Terumasa Omatsu, Kisho Hori, Naoto Ishida, Kohji Maeda, Yumi Yoshida
Summary: This study reports the distribution constant of a target ion and a counter-ion between an aqueous phase and an artificial bilayer lipid membrane, and its impact on the ionic permeability through the membrane. A theoretical formula for ionic permeability based on ion distribution is proposed and validated experimentally. Results show that the ionic permeability is proportional to the concentration of ions inside the membrane as determined by the distribution constant, indicating that the distribution of ions between the aqueous and membrane phases dominates ion transport through the membrane.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Chemistry, Physical
Suleyman Selim Cinaroglu, Philip C. Biggin
Summary: This study comprehensively evaluated the performance of different force fields and water models in predicting host-guest binding enthalpies, discovering a strong sensitivity to their selection. TIP3P and its derivative Bind3P were found to be the best-performing water models for this system, with better performance observed for aliphatic compounds compared to aromatic ones, highlighting the challenges of accurately incorporating aromaticity in simple force fields.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biochemistry & Molecular Biology
Lucy Kate Ladefoged, Rebekka Koch, Philip C. Biggin, Birgit Schiott
Summary: Studying the action of multimodal antidepressant drug vortioxetine (VXT) on different receptors can provide insights into the mechanisms of agonist-antagonist dual behavior and activation without polar interaction with helix 5.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Chemistry, Physical
Zhiyi Wu, Philip C. Biggin
Summary: Absolute binding free-energy calculations play a crucial role in drug design, but accuracy is of utmost importance. This study explores the most suitable approach for simulation boxes containing lipid bilayers, and introduces the Rocklin correction method for lipid bilayer systems.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Article
Biochemistry & Molecular Biology
Harold Grosjean, Mehtap Isik, Anthony Aimon, David Mobley, John Chodera, Frank von Delft, Philip C. Biggin
Summary: A novel crystallographic fragment screening data set was generated and used in the SAMPL7 challenge for protein-ligands. The results show that there is room for improvement in the development of computational tools particularly when applied to fragment-based drug design.
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2022)
Article
Physiology
Adamo S. Mancino, William G. Glass, Yuhao Yan, Philip C. Biggin, Derek Bowie
Summary: Using electrophysiology and molecular dynamics simulations, this study highlights the role of two alternatively spliced residues in the DI S3-S4 linker in channel activation of Nav1.5 and suggests a conserved function in Nav1.4 isoform. Understanding the structural mechanisms of alternative splicing in gating properties of voltage-gated ion channels can provide insights into therapeutic target identification and drug development for related cardiac disorders.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tsung-Han Chou, Max Epstein, Kevin Michalski, Eve Fine, Philip C. Biggin, Hiro Furukawa
Summary: Excitatory signaling mediated by N-methyl-d-aspartate receptor (NMDAR) is critical for brain development and function, as well as for neurological diseases and disorders. Channel blockers of NMDARs are of medical interest owing to their potential for treating depression, Alzheimer's disease, and epilepsy. However, precise mechanisms underlying binding and channel blockade have remained limited owing to challenges in obtaining high-resolution structures at the binding site within the transmembrane domains.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Review
Physiology
David Seiferth, Philip C. Biggin, Stephen J. Tucker
Summary: This article discusses the hydrophobic gating mechanism in ion channels, which regulates ion permeation by controlling the wetness of the pore. The article provides a detailed definition of hydrophobic gating, compares it with other gating mechanisms, and describes the best practices for identifying a hydrophobic gate.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Arvind Kumar, Kayla Kindig, Shanlin Rao, Afroditi-Maria Zaki, Sandip Basak, Mark S. P. Sansom, Philip C. Biggin, Sudha Chakrapani
Summary: This study reveals the structures of Glycine receptors (GlyRs) bound to Delta 9 -tetrahydrocannabinol (THC) using cryo-electron microscopy, providing insights into the therapeutic effects of cannabinoids.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Irfan Alibay, Aniket Magarkar, Daniel Seeliger, Philip Charles Biggin
Summary: The authors evaluate the use of absolute binding free energy calculations in guiding fragment optimization decisions and find that such calculations can effectively guide fragment elaborations to maximize affinity.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Chemistry, Physical
Simon M. Lichtinger, Philip C. Biggin
Summary: The structure of proteins holds the key to understanding their function, but studying the conformational transitions is challenging. The traditional molecular dynamics simulation suffers from starting-state dependence, while the new MEMENTO method provides a solution.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Multidisciplinary Sciences
Eric Gibbs, Emily Klemm, David Seiferth, Arvind Kumar, Serban L. Ilca, Philip C. Biggin, Sudha Chakrapani
Summary: In this study, cryo-EM structures of the α1βGlyR in the presence of an antagonist, agonist, and agonist with a positive allosteric modulator were determined. The structures revealed distinct pore conformations with varying degrees of asymmetry, and the receptors were found to be in closed or desensitized states. Subunit-specific features and characteristics of the extracellular and intracellular domains were also identified. These findings provide a framework for further investigations into the function of this physiologically important channel.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Suleyman Selim Cinaroglu, Philip C. Biggin
Summary: Understanding the thermodynamic signature of protein-peptide binding events is a major challenge in computational chemistry. This study computed the enthalpy of binding for protein-peptide complexes using available experimental data and identified key sampling problems that can be addressed to improve the agreement with experiments. The results show the potential of computational calorimetry in predicting protein-peptide binding enthalpy.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Sueleyman Selim Cinaroglu, Philip C. C. Biggin
Summary: The enthalpic and entropic components of ligand-protein binding free energy are challenging to predict accurately. Recent advances in predicting relative and absolute binding free energies have been successful, but predicting the enthalpic contributions remains challenging. A study evaluating the performance of absolute enthalpy of binding calculations for inhibitors against a bromodomain protein showed good agreement with experimental data and revealed the importance of considering conformational dynamics of a specific loop in improving accuracy.
Article
Chemistry, Physical
David Seiferth, Stephen J. Tucker, Philip C. Biggin
Summary: Transmembrane anion transport by synthetic ionophores is important for understanding endogenous anion transport and has potential therapeutic implications. Computational studies using non-polarizable and polarizable force fields provide insights into the binding properties of anions. The results show solvent dependency and the importance of electrostatics and oxidation status in anion recognition.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Multidisciplinary
Daniel Crusius, Jason R. Schnell, Flaviu Cipcigan, Philip C. Biggin
Summary: Knowing the solution structures of cyclic peptides is crucial for predicting the pharmacokinetic properties in drug discovery. In this study, we introduced the MacroConf dataset and computational workflows to evaluate the performance of current in silico methods in reproducing experimental cyclic peptide solution structures. Our findings show that enhanced sampling molecular dynamics methods, like Gaussian accelerated MD, performed well in reproducing experimental results. Conventional MD suffered from limited sampling, especially for compounds with proline isomerization. Cheminformatics-based conformer generators generated diverse and plausible structures that matched the sampling observed in MD-based methods, but did not provide thermodynamic insights. The presented computational workflow can be easily extended to include new compounds or different simulation methods, serving as a benchmark to improve cyclic peptide conformer generators.
