Article
Multidisciplinary Sciences
Johann Biedermann, Sebastian Braunbeck, Andrew J. R. Plested, Han Sun
Summary: Fast excitatory synaptic transmission in the central nervous system relies on the AMPA-type glutamate receptor (AMPAR), which incorporates a nonselective cation channel. Recent studies combining molecular dynamic simulations and electrophysiology have revealed the ion permeation mechanisms of AMPA receptors, showing that Na+, K+, and Cs+ can permeate at physiological rates through a simple selectivity filter structure. The permissive architecture of the filter allows for rapid, nonselective cation permeation and copermeation by water, with Cs+ slightly more permeant than Na+ due to preferential binding sites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Stefano Stabilini, Anna Menini, Simone Pifferi
Summary: TMEM16F is involved in various physiological processes and acts as both a Ca2+-dependent phospholipid scramblase and a Ca2+-activated ion channel. The ion selectivity of TMEM16F-mediated current depends on the recording configuration, with higher permeability for Na+ in inside-out experiments and a slight preference for Cl over bar permeation in whole-cell recordings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Lijun Liang, Zhisen Zhang, Hongbo Wang, Jia-Wei Shen, Zhe Kong
Summary: Through more than 40 conductance events from microsecond molecular dynamics simulation, soft knock-on ion permeation mediated by water molecules in sodium channels was observed and confirmed. The change of average distance between four oxygen atoms in Glu177-Glu177 was found to play a crucial role in Na+ ion permeation. Exploration of the ionic conductance mechanism may guide the design of ion channel targeted drugs.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Multidisciplinary Sciences
Stephanie Cerceo Page, Srinidhi Rao Sripathy, Federica Farinelli, Zengyou Ye, Yanhong Wang, Daniel J. Hiler, Elizabeth A. Pattie, Claudia Nguyen, Madhavi Tippani, Rebecca L. Moses, Huei-Ying Chen, Matthew Nguyen Tran, Nicholas J. Eagles, Joshua M. Stolz, Joseph L. I. I. I. I. Catallini, Olivia R. Soudry, Dwight Dickinson, Karen F. Berman, Jose A. Apud, Daniel R. Weinberger, Keri Martinowich, Andrew E. Jaffe, Richard E. Straub, Brady J. Maher
Summary: The study analyzed neurons derived from individuals with high polygenic risk scores for schizophrenia (SCZ) and neurotypical individuals, finding that patient-derived neurons exhibited altered electrophysiological measures related to Na+ channel function, action potential interspike interval, and gamma-aminobutyric acid-ergic neurotransmission. These electrophysiological measures predicted core clinical and cognitive features in SCZ patients, potentially offering critical insights for novel therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Peter R. Strege, Luke M. Cowan, Constanza Alcaino, Amelia Mazzone, Christopher A. Ahern, Lorin S. Milescu, Gianrico Farrugia, Arthur Beyder
Summary: Shear stress and patch suction can reversibly alter the kinetic properties and maximum current of NaChBac, suggesting it is mechanosensitive. Structural analysis reveals a large displacement of the intracellular gate, supporting the proposed mechanosensitive mechanism.
Article
Multidisciplinary Sciences
Miriam Hernandez-Morales, Victor Han, Richard H. Kramer, Chunlei Liu
Summary: FeRIC is a magnetogenetic technique using RF alternating magnetic fields to activate TRPV channels and increase cytosolic Ca2+ levels. The interaction between RF and ferritin increases free cytosolic iron levels, triggering the activation of specific pathological channels.
Article
Cardiac & Cardiovascular Systems
Molly O'Reilly, Laura C. Sommerfeld, C. O'Shea, S. Broadway-Stringer, S. Andaleeb, J. S. Reyat, S. N. Kabir, D. Stastny, A. Malinova, D. Delbue, L. Fortmueller, K. Gehmlich, D. Pavlovic, B. Skryabin, A. P. Holmes, P. Kirchhof, L. Fabritz
Summary: This study found that the point mutation M1875T in the SCN5A gene is associated with familial AF. A new mouse model was used to show that this mutation causes gain-of-function of the cardiac sodium channel, resulting in increased atrial excitability.
Article
Biology
Christian J. G. Tessier, Raymond M. Sturgeon, Johnathon R. Emlaw, Gregory D. McCluskey, F. Javier Perez-Areales, Corrie J. B. daCosta
Summary: Human adult muscle-type acetylcholine receptors are heteropentameric ion channels formed from different subunits, but they share a common ancestral homopentameric origin. A reconstructed ancestral muscle-type beta-subunit can form spontaneously open homopentameric ion channels, demonstrating that the function of the receptor is independent of agonist and does not require complex heteropentameric architecture.
Article
Biochemistry & Molecular Biology
Yipeng Cao, Rui Yang, Jiana Sun, Wenwen Zhang, Imshik Lee, Wei Wang, Xiangfei Meng
Summary: The study found that both pSLN and T18A pentameric channels form stable hydrophobic ligand-gated channels, and transmembrane voltage has a positive effect on the permeability of water molecules and ions. By using pSLN and T18A, the study provides useful information on the pore-forming mechanism of SLN and deepens our understanding of the regulatory mechanisms underlying the permeation of ions and water molecules in the pentameric SLN channel.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Nanoscience & Nanotechnology
Kumar Saurabh, Maxim Solovchuk
Summary: The study focuses on fluid-ion transport in a nanochannel and aims to understand the impact of physical phenomena and medium properties on the flow. Mathematical models, including the fourth order Poisson-Nernst-Planck-Bikerman and Navier-Stokes equations, are used to describe the system. These models consider various interactions, particle size, and polarization effects. The validity of the models is confirmed through analytical and experimental comparisons, and the impact of different factors on fluid velocity is analyzed.
Article
Biochemistry & Molecular Biology
Karl Josef Foehr, Michael Rapp, Michael Fauler, Thomas Zimmer, Bettina Jungwirth, David Alexander Christian Messerer
Summary: Aripiprazole has been identified as a potent blocker of the dominant voltage-gated sodium channel of heart muscle. Its interactions with the channel differ depending on the state, with weaker affinity for the resting state and stronger affinity for the inactivated state.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Hui-Yuan Zhang, Qin Xu, Dong-Qing Wei
Summary: Charge plays a key role in passive permeation of small molecules, and simulations on water and sulfide molecules reveal distinct characteristics in their permeation processes, with free energy highly correlated with the hydrophilic shell.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Biology
John R. Strikwerda, Steven M. Sine
Summary: This research on muscle nicotinic receptors reveals a coupling between channel gating and ion permeation through structural perturbation, showing that a charge-neutralizing mutation can suppress channel gating and impact unitary current amplitude. The study also demonstrates that the power spectrum and current relaxations are described by a theory where structural motions contribute to both channel gating and ion conduction. Coupling is manifested as a transient increase in open channel current upon channel opening and a decrease upon channel closing.
Article
Chemistry, Multidisciplinary
David Roesel, Maksim Eremchev, Chetan S. Poojari, Jochen S. Hub, Sylvie Roke
Summary: A direct link between membrane potential fluctuations and divalent ion transport has been discovered, and it has been shown through molecular dynamics simulations and experimental results that pore formation induced by an ion-induced electrostatic field is a viable mechanism for unassisted ion transport.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Physics, Mathematical
Weizhang Huang, Weishi Liu, Yufei Yu
Summary: Ionic flow is crucial for cell communication, with permanent charge and boundary conditions affecting flow properties. Analytical and numerical studies reveal complex phenomena of permanent charge effects and transitions between small and large charges.
COMMUNICATIONS IN COMPUTATIONAL PHYSICS
(2021)
Article
Chemistry, Medicinal
Michael J. Nutt, Yeung Sing Yee, Amanda Buyan, Neil Andrewartha, Ben Corry, George C. T. Yeoh, Scott G. Stewart
Summary: Novel thalidomide derivatives exhibit selective antiproliferative effects on tumorigenic liver progenitor cells, with significant inhibition of LPC migration and reduction of STAT3 phosphorylation, suggesting involvement of the IL-6/JAK/STAT3 axis in their mode of action.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biophysics
Elaine Tao, Ben Corry
Summary: Voltage-gated sodium channels play a crucial role in the electrical activity of nerve and muscle cells, with humans having nine different subtypes. Research indicates that there are four lateral fenestrations within these channels influencing the access of pore blockers. Although there are structural differences among the subtypes, a common pattern in the dimensions of the fenestrations has been observed, with one particular fenestration appearing most favorable for drug access in all subtypes. These findings are significant for the development of pharmacological treatments and the analysis of disease mutations in sodium channel subtypes.
BIOPHYSICAL JOURNAL
(2022)
Review
Biophysics
Yiechang Lin, Amanda Buyan, Ben Corry
Summary: Piezo1 is a mechanically gated ion channel that plays a critical role in converting mechanical stimuli into electrical signals and regulating blood pressure. Recent studies have used cryo-EM structures and computational simulations to investigate the behavior of Piezo1 at an atomistic level. This review summarizes papers that combine computational techniques with experimental approaches to study Piezo1, discussing the limitations of using computational techniques and providing potential directions for future research.
BIOPHYSICAL REVIEWS
(2022)
Article
Chemistry, Physical
Alice J. Hutchinson, Juan F. Torres, Ben Corry
Summary: This study aims to improve the accuracy of MD thermodiffusion models by assessing different water models in recreating thermodiffusion in aqueous NaCl solutions. By comparing the modeled parameters to experimental values, TIP3P-FB is determined to be the best water model.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Grant J. Brown, Pablo F. Canete, Hao Wang, Arti Medhavy, Josiah Bones, Jonathan A. Roco, Yuke He, Yuting Qin, Jean Cappello, Julia I. Ellyard, Katharine Bassett, Qian Shen, Gaetan Burgio, Yaoyuan Zhang, Cynthia Turnbull, Xiangpeng Meng, Phil Wu, Eun Cho, Lisa A. Miosge, T. Daniel Andrews, Matt A. Field, Denis Tvorogov, Angel F. Lopez, Jeffrey J. Babon, Cristina Aparicio Lopez, Africa Gonzalez-Murillo, Daniel Clemente Garulo, Virginia Pascual, Tess Levy, Eric J. Mallack, Daniel G. Calame, Timothy Lotze, James R. Lupski, Huihua Ding, Tomalika R. Ullah, Giles D. Walters, Mark E. Koina, Matthew C. Cook, Nan Shen, Carmen de Lucas Collantes, Ben Corry, Michael P. Gantier, Vicki Athanasopoulos, Carola G. Vinuesa
Summary: Enhanced Toll-like receptor 7 (TLR7) signaling has been associated with human systemic autoimmune disease, but evidence of TLR7 gene variants causing lupus is lacking. In this study, researchers identified a newly described TLR7(Y264H) variant that increased sensing of guanosine and 2',3'-cGMP and was sufficient to cause lupus in mice. Enhanced TLR7 signaling was shown to drive aberrant B cell survival and the accumulation of specific B cell subsets, while deficiency of the downstream adapter protein MyD88 rescued autoimmunity and all phenotypes. The study highlights the importance of TLR7 and guanosine-containing self-ligands in the pathogenesis of lupus and suggests potential therapeutic targets.
Article
Biochemistry & Molecular Biology
Sarah Heckmatt Shafik, Sashika Natasha Richards, Ben Corry, Rowena Elizabeth Martin
Summary: Polymorphisms in the Pfmdr1 and Pfcrt genes alter the susceptibility of the malaria parasite to antimalarial drugs. This study provides insights into the mechanisms by which these genes contribute to drug resistance and explains the phenomenon of collateral drug sensitivity.
Article
Biophysics
Amanda Buyan, D. W. Allender, Ben Corry, M. Schick
Summary: We investigated the effects of Piezo1 protein insertion on the lipid distribution in the plasma membrane. Coarse-grained molecular dynamics simulations revealed that the outer leaflet experienced major changes, with increased cholesterol and decreased phosphatidylcholine and sphingomyelin near Piezo1. The inner leaflet showed slight decreases in cholesterol and phosphatidylethanolamine, slight increase in phosphatidylserine, and significant decrease in phosphatidylcholine near the protein. These findings can be explained by a theoretical model that considers the coupling between actual curvatures and composition-dependent spontaneous curvatures of the leaflets, as well as the influence of cholesterol on the spontaneous curvatures of phospholipids.
BIOPHYSICAL JOURNAL
(2023)
Article
Physiology
Yiechang Lin, Amanda Buyan, Ben Corry
Summary: Piezo2, a membrane protein, interacts with lipids in the membrane and forms long-term interactions with specific lipids at functionally relevant sites. It plays critical roles in sensing mechanical signals and regulating various physiological functions.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Review
Physics, Multidisciplinary
C. Guardiani, F. Cecconi, L. Chiodo, G. Cottone, P. Malgaretti, L. Maragliano, M. L. Barabash, G. Camisasca, M. Ceccarelli, B. Corry, R. Roth, A. Giacomello, B. Roux
Summary: Ion channels act as gates on cellular membranes to ensure selective ion transport, serving as the molecular mechanism for basic biological functions like nerve signal transmission and muscle contraction. Recent computational research on ion channels reviews theoretical advances, simulation approaches, and modeling techniques, including applications to understand permeation, selectivity, and gating mechanisms in biological and model channels.
ADVANCES IN PHYSICS-X
(2022)
Article
Multidisciplinary Sciences
Deyun Qiu, Jinxin V. Pei, James E. O. Rosling, Vandana Thathy, Dongdi Li, Yi Xue, John D. Tanner, Jocelyn Sietsma Penington, Yi Tong Vincent Aw, Jessica Yi Han Aw, Guoyue Xu, Abhai K. Tripathi, Nina F. Gnadig, Tomas Yeo, Kate J. Fairhurst, Barbara H. Stokes, James M. Murithi, Krittikorn Kumpornsin, Heath Hasemer, Adelaide S. M. Dennis, Melanie C. Ridgway, Esther K. Schmitt, Judith Straimer, Anthony T. Papenfuss, Marcus C. S. Lee, Ben Corry, Photini Sinnis, David A. Fidock, Giel G. van Dooren, Kiaran Kirk, Adele M. Lehane
Summary: The G358S mutation in PfATP4 decreases the sensitivity of ATP4 to inhibition by cipargamin and (+)-SJ733, thereby protecting parasites from disruption of Na+ regulation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Anna Robinson, Elaine Tao, Teresa Neeman, Benjamin Kaehler, Ben Corry
Summary: Researchers constructed a homology model of the hSkMNaV1.4 channel to investigate the structural and functional implications of the 59-residue DIS5-S6 linker peptide. The linker peptide, unique to mammalian skeletal muscle sodium ion channels, was found to fold into a compact configuration and may play a critical role in channel gating.
Article
Engineering, Chemical
Zhongjin He, Ben Corry
Summary: The study reveals that under electric fields, the biomimetic nanopore conducts Na+ preferentially and slows down the passage of Ca2+ by selectively binding it to the carboxylate groups. In strong electric fields, a Cl- concentration polarization layer forms on one side of the nanopore, leading to the formation of stable clusters of Cl- and Ca2+ pairs bound at the carboxylate groups, which severely hinders Cl- transport and occasionally suspends the transport of cations. These findings provide design principles and implications for the fabrication of nanoporous graphene membranes for separation applications, such as heavy metal removal from wastewater.
Article
Multidisciplinary Sciences
Zijing Zhou, Xiaonuo Ma, Yiechang Lin, Delfine Cheng, Navid Bavi, Genevieve A. Secker, Jinyuan Vero Li, Vaibhao Janbandhu, Drew L. Sutton, Hamish S. Scott, Mingxi Yao, Richard P. Harvey, Natasha L. Harvey, Ben Corry, Yixiao Zhang, Charles D. Cox
Summary: In this study, the researchers identified MDFIC and MDFI as interacting partners of the PIEZO1/2 channels. These proteins bind to the PIEZO1/2 channels and regulate their inactivation. The researchers also determined the interaction site of MDFIC in the PIEZO1 pore module using cryogenic electron microscopy, providing insights into the gating kinetics of endogenous Piezo channels and potential mechanisms involved in human lymphatic vascular disease.
Article
Biophysics
Amanda Buyan, Aidan A. Whitfield, Ben Corry
Summary: Voltage-gated sodium channels are crucial for encoding and transmitting electrical signals in nerve and muscle cells. Currently, drugs that aim to inhibit these channels lack subtype specificity, with some potential differences observed in how different drugs bind to the channels based on molecular dynamics simulations.
BIOPHYSICAL JOURNAL
(2021)
Article
Chemistry, Physical
Vito F. Palmisano, Carlos Gomez-Rodellar, Hannah Pollak, Gustavo Cardenas, Ben Corry, Shirin Faraji, Juan J. Nogueira
Summary: The activity of voltage-gated ion channels can be controlled by photoswitches binding inside their internal cavity and subsequent light irradiation. Through simulations, it was found that azobenzene and p-diaminoazobenzene can bind to the human Na(v)1.4 channel in the inactivated state with stable binding pockets. The binding is mainly controlled by the balance between favorable hydrophobic interactions and unfavorable polar solvation energy.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
