Article
Multidisciplinary Sciences
Tim Hempel, Mauricio J. del Razo, Christopher T. Lee, Bryn C. Taylor, Rommie E. Amaro, Frank Noe
Summary: In this study, a technique called independent Markov decomposition (IMD) is introduced, which leverages weak coupling between subsystems to compute a global kinetic model without requiring sampling of all combinatorial states of subsystems. It is demonstrated that IMD models can reproduce experimental conductance measurements with significant reduction in sampling compared to a standard approach. The study also proposes a method to find the optimal partition of all-atom protein simulations into weakly coupled subunits.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Kitty Hendriks, Carl Oester, Chaowei Shi, Han Sun, Adam Lange
Summary: The study demonstrates that K+-selective mutants lose selectivity filter stability under Na+ conditions without collapsing into a defined structure, and structural changes occur.
Compared to the non-selective wild-type NaK channel, the stronger link between the selectivity filter and the pore helix in K+-selective mutants reduces the ion-dependent conformational flexibility of the selectivity filter.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Physical
Emmanuelle Bignon, Marco Marazzi, Antonio Monari
Summary: This study reports on how the SARS-CoV-2 ORF3a permeabilizes the lipid membrane in a model lipid bilayer, forming a water channel to ensure ion transport. The important role of ORF3a in the viral cycle and its high conservation among coronaviruses may make it a target for future antiviral development.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Jun Lu, Gengping Jiang, Huacheng Zhang, Binbin Qian, Haijin Zhu, Qinfen Gu, Yuan Yan, Jefferson Zhe Liu, Benny D. Freeman, Lei Jiang, Huanting Wang
Summary: An artificial sodium channel with unprecedented Na+/K+ selectivity and Na+/Li+ selectivity was developed by confining 4'-aminobenzo-15-crown-5 ethers (15C5s) into a metal-organic framework subnanochannel (MOFSNC). This study proposed a co-ion-responsive single-file transport mechanism for the preferential transport of Na+ over K+ in the 15C-MOFSNC. The findings offer an alternative strategy for developing single-ion selective channels and membranes.
Article
Biology
Cathrine Bergh, Stephanie A. Heusser, Rebecca Howard, Erik Lindahl
Summary: The study utilized enhanced sampling to simulate the pH-gated channel GLIC and construct Markov state models of gating, revealing differential effects of protonation and mutation on channel states, estimation of open probabilities and transition rates, as well as state- and protonation-dependent symmetrization.
Article
Biochemistry & Molecular Biology
Liuba Mazzanti, Tap Ha-Duong
Summary: The early characterization of drug membrane permeability is crucial for pharmaceutical developments, especially for therapeutic peptides. Further research is needed to understand the relationship between sequence, structure, dynamics, and permeability of peptides for efficient therapeutic peptide design. This study compares two physical models for estimating the permeability coefficient of a benchmark peptide and assesses their accuracy and computational cost.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Andrei Mironenko, Ulrich Zachariae, Bert L. de Groot, Wojciech Kopec
Summary: Potassium channels play critical roles in physiological processes by providing a selective permeation route for K+ ions. The structure of the selectivity filter has been determined at atomic resolution, but the molecular mechanism of K+ ions permeation remains unclear. Various proposed mechanisms of ion permeation are discussed, with critical evaluation against available data.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Raktim N. Roy, Kitty Hendriks, Wojciech Kopec, Saeid Abdolvand, Kevin L. Weiss, Bert L. de Groot, Adam Lange, Han Sun, Leighton Coates
Summary: The crystallographic study of the sodium potassium ion channel (NaK) identified differences in conformation of the selectivity filter and inner helix among the four subunits forming the ion channel. The study also revealed a unique side-entry ion-conduction pathway for Na+ permeation in NaK. Additionally, NMR and molecular dynamics simulations confirmed the dynamic nature of the selectivity filter and inner helix, highlighting their importance in efficient ion conduction through the non-selective ion channel of NaK.
Article
Chemistry, Physical
Stefan Milenkovic, Igor V. Bodrenko, Armando Carpaneto, Matteo Ceccarelli
Summary: This article discusses the important role of mammalian two-pore channels in maintaining cellular life processes, particularly the significance of hTPC2 in viral infections. Through molecular simulations, a model for sodium ion transport is proposed.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Review
Biochemistry & Molecular Biology
Matthew C. Chan, Diwakar Shukla
Summary: The passage discusses the importance of membrane transporters in maintaining ion and molecule flux, as well as the challenges of characterizing conformational transitions in these proteins. It highlights the use of adaptive sampling and Markov state models to overcome these challenges and study the structure-function mechanisms of large, complex membrane transporters.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Review
Materials Science, Multidisciplinary
Minmin Li, Yuchen Cao, Yuting Xiong, Guangyan Qing
Summary: Biological ion channels have asymmetries in structure and charge distribution, which enable them to perform diverse activities such as signal transduction and cell motility. Inspired by this, researchers have been pursuing artificial ion channels with comparable functions. However, current homogeneous nanochannels have not been able to achieve similar rewards. Hierarchically engineered heterogeneous nanochannels, on the other hand, have shown promising properties such as ion selectivity and permeability, and have found applications in selective ion transport, energy conversion, biomolecular separation, and detection. In this article, recent advances in these hierarchically engineered nanochannel systems are reviewed, with a focus on pore-on-pore and pore-in-pore structures, and their potential applications are discussed.
NPG ASIA MATERIALS
(2023)
Article
Multidisciplinary Sciences
Seu-Na Lee, Hwa-Jin Cho, Hyeongseop Jeong, Bumhan Ryu, Hyuk-Joon Lee, Minsoo Kim, Jejoong Yoo, Jae-Sung Woo, Hyung Ho Lee
Summary: Cx36, responsible for signal transmission in electrical synapses, forms interneuronal gap junctions. Cryo-EM structures of Cx36 reveal a closed state with obstructed channel pores and excluded N-terminal helices, and an open state with acidic pore and weakened protomer-protomer interaction. Lipids may play a potential role in Cx36 channel gating.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Ion Mitxelena, Xabier Lopez, David de Sancho
Summary: Markov state models (MSMs) are a preferred method for analyzing and interpreting molecular dynamics simulations of conformational transitions in biopolymers. By utilizing hierarchical density-based clustering, it is possible to define slow dynamics more effectively and consistently with the assumption of Markovianity.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Biophysics
David Kleinheinz, Chiara D'Onofrio, Colm Carraher, Ulrich Ramach, Bernhard Schuster, Anil Bozdogan, Wolfgang Knoll, Jakob Andersson
Summary: Membrane proteins are crucial drug targets, but studying them is challenging due to the complexity of the cellular membrane. Tethered membrane systems can replicate basic properties of the cellular membrane, making them ideal for studying membrane proteins thanks to their high electrical resistance and stability.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Physics, Multidisciplinary
Salvatore M. Cosseddu, Eunju Julia Choe, Igor A. Khovanov
Summary: In the potassium ion channel KcsA, a strongly correlated dynamical network of interacting residues centered on the aspartate D80 plays a key role in regulating the state of the channel. This network affects ion permeation and is influenced by the locations of ions and water molecules inside the selectivity filter. The necessity of anionic lipids for channel functioning is explained by interactions between lipids and specific arginine residues that stabilize the selectivity filter structure.
Article
Multidisciplinary Sciences
Charles J. Buchanan, Ben Gaunt, Peter J. Harrison, Yun Yang, Jiwei Liu, Aziz Khan, Andrew M. Giltrap, Audrey Le Bas, Philip N. Ward, Kapil Gupta, Maud Dumoux, Tiong Kit Tan, Lisa Schimaski, Sergio Daga, Nicola Picchiotti, Margherita Baldassarri, Elisa Benetti, Chiara Fallerini, Francesca Fava, Annarita Giliberti, Panagiotis Koukos, Matthew J. Davy, Abirami Lakshminarayanan, Xiaochao Xue, Georgios Papadakis, Lachlan P. Deimel, Virginia Casablancas-Antras, Timothy D. W. Claridge, Alexandre M. J. J. Bonvin, Quentin J. Sattentau, Simone Furini, Marco Gori, Jiandong Huo, Raymond J. Owens, Christiane Schaffitzel, Imre Berger, Alessandra Renieri, James H. Naismith, Andrew J. Baldwin, Benjamin G. Davis
Summary: This study utilizes universal saturation transfer analysis to reveal the interaction between the novel coronavirus and glycan compounds, and identifies protein mutations related to pathogenicity and zoonosis.
Article
Virology
Kristina Zguro, Margherita Baldassarri, Francesca Fava, Giada Beligni, Sergio Daga, Roberto Leoncini, Lucrezia Galasso, Michele Cirianni, Stefano Rusconi, Matteo Siano, Daniela Francisci, Elisabetta Schiaroli, Sauro Luchi, Giovanna Morelli, Enrico Martinelli, Massimo Girardis, Stefano Busani, Saverio Giuseppe Parisi, Sandro Panese, Carmelo Piscopo, Mario Capasso, Danilo Tacconi, Chiara Spertilli Raffaelli, Annarita Giliberti, Giulia Gori, Peter D. Katsikis, Maria Lorubbio, Paola Calzoni, Agostino Ognibene, Monica Bocchia, Monica Tozzi, Alessandro Bucalossi, Giuseppe Marotta, Simone Furini, Alessandra Renieri, Chiara Fallerini
Summary: This study reports the host genetic determinants of thrombosis in COVID-19 and identifies a rare form of the disease caused by specific genetic variants. The findings have clinical relevance for the development of targeted treatments to inhibit platelet and leukocyte activities.
Article
Neurosciences
Amjad Khan, Lucia Pia Bruno, Fadhel Alomar, Muhammad Umair, Anna Maria Pinto, Abid Ali Khan, Alamzeb Khan, Alessandra Fabbiani, Kristina Zguro, Simone Furini, Maria Antonietta Mencarelli, Alessandra Renieri, Sara Resciniti, Karla A. Pena-Guerra, Francisco J. Guzman-Vega, Stefan T. Arold, Francesca Ariani, Shahid Niaz Khan
Summary: Whole exome sequencing is a valuable tool for discovering novel candidate genes for intellectual disability and autism spectrum disorders. This study provides the first evidence associating SPTBN5 gene variants with neurodevelopmental phenotypes and identifies the clinical traits associated with these variants.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Letter
Genetics & Heredity
Lucia Pia Bruno, Gabriella Doddato, Margherita Baldassarri, Caterina Lo Rizzo, Sara Resciniti, Mirella Bruttini, Lista Mirjam, Kristina Zguro, Simone Furini, Maria Antonietta Mencarelli, Alessandra Renieri, Francesca Ariani
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Guillaume Butler-Laporte, Gundula Povysil, Jack A. Kosmicki, Elizabeth T. Cirulli, Theodore Drivas, Simone Furini, Chadi Saad, Axel Schmidt, Pawel Olszewski, Urszula Korotko, Mathieu Quinodoz, Elifnaz Celik, Kousik Kundu, Klaudia Walter, Junghyun Jung, Amy D. Stockwell, Laura G. Sloofman, Daniel M. Jordan, Ryan C. Thompson, Diane Del Valle, Nicole Simons, Esther Cheng, Robert Sebra, Eric E. Schadt, Seunghee Kim-Schulze, Sacha Gnjatic, Miriam Merad, Joseph D. Buxbaum, Noam D. Beckmann, Alexander W. Charney, Bartlomiej Przychodzen, Timothy Chang, Tess D. Pottinger, Ning Shang, Fabian Brand, Francesca Fava, Francesca Mari, Karolina Chwialkowska, Magdalena Niemira, Szymon Pula, J. Kenneth Baillie, Alex Stuckey, Antonio Salas, Xabier Bello, Jacobo Pardo-Seco, Alberto Gomez-Carballa, Irene Rivero-Calle, Federico Martinon-Torres, Andrea Ganna, Konrad J. Karczewski, Kumar Veerapen, Mathieu Bourgey, Guillaume Bourque, Robert Jm Eveleigh, Vincenzo Forgetta, David Morrison, David Langlais, Mark Lathrop, Vincent Mooser, Tomoko Nakanishi, Robert Frithiof, Michael Hultstrom, Miklos Lipcsey, Yanara Marincevic-Zuniga, Jessica Nordlund, Kelly M. Schiabor Barrett, William Lee, Alexandre Bolze, Simon White, Stephen Riffle, Francisco Tanudjaja, Efren Sandoval, Iva Neveux, Shaun Dabe, Nicolas Casadei, Susanne Motameny, Manal Alaamery, Salam Massadeh, Nora Aljawini, Mansour S. Almutairi, Yaseen M. Arabi, Saleh A. Alqahtani, Fawz S. Al Harthi, Amal Almutairi, Fatima Alqubaishi, Sarah Alotaibi, Albandari Binowayn, Ebtehal A. Alsolm, Hadeel El Bardisy, Mohammad Fawzy, Fang Cai, Nicole Soranzo, Adam Butterworth, Daniel H. Geschwind, Stephanie Arteaga, Alexis Stephens, Manish J. Butte, Paul C. Boutros, Takafumi N. Yamaguchi, Shu Tao, Stefan Eng, Timothy Sanders, Paul J. Tung, Michael E. Broudy, Yu Pan, Alfredo Gonzalez, Nikhil Chavan, Ruth Johnson, Bogdan Pasaniuc, Brian Yaspan, Sandra Smieszek, Carlo Rivolta, Stephanie Bibert, Pierre-Yves Bochud, Maciej Dabrowski, Pawel Zawadzki, Mateusz Sypniewski, Elzbieta Kaja, Pajaree Chariyavilaskul, Voraphoj Nilaratanakul, Nattiya Hirankarn, Vorasuk Shotelersuk, Monnat Pongpanich, Chureerat Phokaew, Wanna Chetruengchai, Katsushi Tokunaga, Masaya Sugiyama, Yosuke Kawai, Takanori Hasegawa, Tatsuhiko Naito, Ho Namkoong, Ryuya Edahiro, Akinori Kimura, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, Yukinori Okada, Seiya Imoto, Satoru Miyano, Serghei Mangul, Malak S. Abedalthagafi, Hugo Zeberg, Joseph J. Grzymski, Nicole L. Washington, Stephan Ossowski, Kerstin U. Ludwig, Eva C. Schulte, Olaf Riess, Marcin Moniuszko, Miroslaw Kwasniewski, Hamdi Mbarek, Said I. Ismail, Anurag Verma, David B. Goldstein, Krzysztof Kiryluk, Alessandra Renieri, Manuel A. R. Ferreira, J. Brent Richards
Summary: Host genetics play a crucial role in COVID-19 outcomes, and studying rare variants can provide additional insights. A study combining whole-exome and whole-genome sequencing from 21 cohorts across 12 countries found that carrying a rare deleterious variant in the TLR7 gene on chromosome X is associated with a 5.3-fold increase in severe disease. This association is consistent across genders, further supporting TLR7 as a genetic determinant of severe COVID-19.
Article
Biology
Anthony Onoja, Nicola Picchiotti, Chiara Fallerini, Margherita Baldassarri, Francesca Fava, Francesca Colombo, Francesca Chiaromonte, Alessandra Renieri, Simone Furini, Francesco Raimondi
Summary: A multifaceted computational strategy identified 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of an Italian patient cohort. These variants, along with age, gender, and specific diseases, can predict COVID-19 severity with high accuracy. The study also revealed immune and inflammatory processes related to viral infection response, as well as other cross-talking signaling pathways, providing new opportunities for treatment and patient stratification.
COMMUNICATIONS BIOLOGY
(2022)
Correction
Biochemistry & Molecular Biology
Sergio Daga, Francesco Donati, Katia Capitani, Susanna Croci, Rossella Tita, Annarita Giliberti, Floriana Valentino, Elisa Benetti, Chiara Fallerini, Francesca Niccheri, Margherita Baldassarri, Maria Antonietta Mencarelli, Elisa Frullanti, Simone Furini, Silvestro Giovanni Conticello, Alessandra Renieri, Anna Maria Pinto
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Correction
Biochemistry & Molecular Biology
Susanna Croci, Miriam Lucia Carriero, Katia Capitani, Sergio Daga, Francesco Donati, Elisa Frullanti, Vittoria Lamacchia, Rossella Tita, Annarita Giliberti, Floriana Valentino, Elisa Benetti, Annalisa Ciabattini, Simone Furini, Caterina Lo Rizzo, Anna Maria Pinto, Silvestro Giovanni Conticello, Alessandra Renieri, Ilaria Meloni
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Chemistry, Medicinal
Francesco Pettini, Carmen Domene, Simone Furini
Summary: Fast C-type inactivation confers distinctive functional properties to the hERG potassium channel, but its mechanism and association with cardiac arrythmias are of paramount importance. Two models have been proposed for C-type inactivation in K+ channels, and this study used molecular dynamics simulations to investigate the mechanism in hERG. The findings suggest that C-type inactivation in hERG involves a widening of the extracellular entrance of the channel rather than a closure of the selectivity filter.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Correction
Oncology
Chiara Fallerini, Sergio Daga, Elisa Benetti, Nicola Picchiotti, Kristina Zguro, Francesca Catapano, Virginia Baroni, Simone Lanini, Alessandro Bucalossi, Giuseppe Marotta, Francesca Colombo, Margherita Baldassarri, Francesca Fava, Giada Beligni, Laura Di Sarno, Diana Alaverdian, Maria Palmieri, Susanna Croci, Andrea M. M. Isidori, Simone Furini, Elisa Frullanti, Alessandra GEN-COVID Multictr Study, Alessandra Renieri, Francesca Mari
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Biology
Eider Nunez, Frederick Jones, Arantza Muguruza-Montero, Janire Urrutia, Alejandra Aguado, Covadonga Malo, Ganeko Bernardo-Seisdedos, Carmen Domene, Oscar Millet, Nikita Gamper, Alvaro Villarroel, Henry M. Colecraft
Summary: Neuronal K(V)7 channels are highly sensitive to reactive oxygen species, and the S2S3 linker of the voltage sensor plays a crucial role in redox modulation of the channels. Recent structural studies have revealed interactions between this linker and the Ca2+-binding loop of calmodulin, specifically the EF3 hand, which is essential for the signaling. Disrupting Ca2+ binding to EF3 abolishes the oxidation-induced enhancement of K(V)7.4 currents. Furthermore, the loading of EF3 with Ca2+ is critical for the reorientation of the AB fork, which translates the Ca2+ signals.
Article
Psychiatry
Flavia Privitera, Maria A. Trusso, Floriana Valentino, Gabriella Doddato, Chiara Fallerini, Giulia Brunelli, Romina D'Aurizio, Simone Furini, Arianna Goracci, Andrea Fagiolini, Francesca Mari, Alessandra Renieri, Francesca Ariani
Summary: This study focuses on a large family with 12 members affected by bipolar disorder. Through whole-exome sequencing, certain genes, including CLN6 and ZNF92, were identified as having variations associated with the disorder. The findings suggest that heterozygous carriers of CLN6 may develop bipolar disorder later in life if combined with additional variants in ZNF92.
BRAZILIAN JOURNAL OF PSYCHIATRY
(2023)
Article
Chemistry, Medicinal
Francesco Pettini, Carmen Domene, Simone Furini
Summary: The study of the inactivation mechanism of hERG is crucial due to its association with cardiac arrhythmias. Two models, namely, the closure of the selectivity filter and the widening of the extracellular portion of the selectivity filter, have been proposed to describe C-type inactivation in potassium channels. Molecular dynamics simulations revealed that the extracellular entrance of hERG widens during inactivation, supporting the hypothesis of widening of the extracellular entrance rather than closure of the selectivity filter.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)