Article
Chemistry, Medicinal
Nitin A. Patil, Wendong Ma, Xukai Jiang, Xiaoji He, Heidi H. Yu, Hasini Wickremasinghe, Jiping Wang, Philip E. Thompson, Tony Velkov, Kade D. Roberts, Jian Li
Summary: Polymyxins, including polymyxin B and colistin, are used as a last resort to treat life-threatening multidrug-resistant Gram-negative bacterial infections. However, their clinical use is limited by toxicity and increasing resistance. This study explores the role of the conserved position 10 threonine residue in polymyxin's structure and reveals the requirements for antibacterial activity. These findings provide vital information for developing safer and more effective next-generation polymyxin antibiotics.
JOURNAL OF MEDICINAL CHEMISTRY
(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, Physical
Zun Wang, Hongfei Wu, Lixin Sun, Xinheng He, Zhirong Liu, Bin Shao, Tong Wang, Tie-Yan Liu
Summary: Machine learning force fields (MLFFs) have become a cost-effective alternative to ab initio molecular dynamics (MD) simulations. However, they suffer from generalization and robustness issues. To address this, we proposed global force metrics and fine-grained metrics to systematically measure MLFFs. We evaluated three state-of-the-art MLFFs on different molecules and analyzed the relationship between force metrics and simulation stability.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Thomas J. Oweida, Ho Shin Kim, Johnny M. Donald, Abhishek Singh, Yaroslava G. Yingling
Summary: This study assessed the accuracy and applicability of existing Amber force fields for all-atom simulations of ssDNA, and found that the Amber ff99 force field in the IGB5 or IGB8 implicit solvent and the bsc1 force field in the explicit TIP3P solvent had the best agreement with experimental data.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Physical
Jung Cho, Yifeng Yun, Hongyi Xu, Junliang Sun, Allen W. Burton, Karl G. Strohmaier, Gene Terefenko, Hilda Vroman, Mobae Afeworki, Guang Cao, Hao Wang, Xiaodong Zou, Tom Willhammar
Summary: The structure of novel medium-pore borosilicate zeolite EMM-25 was determined using continuous rotation electron diffraction (cRED). A new ammonium dication OSDA was found to reduce synthesis time significantly, and structural disorder in the form of swinging zigzag chains was observed in the EMM-25 framework.
CHEMISTRY OF MATERIALS
(2021)
Article
Chemistry, Multidisciplinary
Maryam Yekefallah, Carver A. Rasberry, Evan J. Van Aalst, Holley P. Browning, Reza Amani, Derek B. Versteeg, Benjamin J. Wylie
Summary: Potassium channels are regulated by allosteric communication between the helical bundle crossing and the selectivity filter. KirBac1.1 is a bacterial potassium channel that is gated by the anionic phospholipid ligand PG. Site-directed mutagenesis and molecular dynamics simulations were used to investigate the gating mechanism and allosteric network of KirBac1.1.
Article
Chemistry, Physical
Taichi Inagaki, Shinji Saito
Summary: In this paper, a new hybrid method called potential scaling HMC (PS-HMC) is introduced to study complex chemical processes. By modulating the trajectory and gradually flattening the potential energy surface, the PS-HMC method is capable of constructing the canonical ensemble with a multimodal distribution. Applications to different molecular processes demonstrate the feasibility and features of this new method.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Physical
C. Calero, M. Diaz-Morata, I. Pagonabarraga
Summary: Depletion interactions between discoidal colloids can induce self-assembly into columnar aggregates, with important implications in colloidal systems like blood. By studying the equilibrium state of discoidal colloids in a solution of smaller depletant particles and developing a thermodynamic model based on self-assembly theory, the validity of the model can be tested using Langevin simulations. Additionally, considering the effect of attractive interactions between depletant and discoidal particles can lead to a re-entrant dependence of aggregation with temperature.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Multidisciplinary Sciences
Oliver T. Unke, Stefan Chmiela, Michael Gastegger, Kristof T. Schuett, Huziel E. Sauceda, Klaus-Robert Mueller
Summary: SpookyNet is a deep neural network that addresses the issue of electronic degrees of freedom and nonlocality typically ignored in machine-learned force fields. By incorporating chemically meaningful inductive biases and analytical corrections into the network architecture, SpookyNet can improve performance in quantum chemistry and fill important gaps in machine learning models.
NATURE COMMUNICATIONS
(2021)
Article
Polymer Science
Yaguang Sun, Kaiwei Wan, Wenhui Shen, Jianxin He, Tong Zhou, Hui Wang, Hua Yang, Xinghua Shi
Summary: Recycling and reprocessing of conventional thermosetting polymers have gained attention due to environmental concerns. This study focuses on covalent adaptable networks (CANs) which incorporate functional groups capable of reversible exchange reactions into polymer networks, altering the topology arrangement and achieving stress relaxation. The researchers developed a machine-learning force field to describe the exchange reactions of polyimine CANs and provided insights into reaction mechanisms and energy profiles through enhanced sampling methods.
Article
Chemistry, Physical
Andras Baranyai
Summary: This paper discusses the properties of alkali and halide ions in molecular simulation and presents a set of potentials to estimate their internal energy, density, and melting temperature. The ions have non-polarizable Gaussian charges with r(-6) attraction and exponential repulsion. The results and the difficulties of the process are discussed.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Chemistry, Multidisciplinary
Shuji Fujisawa, Kazuho Daicho, Ayhan Yurtsever, Takeshi Fukuma, Tsuguyuki Saito
Summary: All-atom molecular dynamics simulations and atomic force microscopy were used to study the structural dynamics of single nanocellulose during drying. It was discovered that the twist morphology of nanocellulose becomes localized along the fibril axis in the final stage of drying. Conformational changes at C6 hydroxymethyl groups and glycoside bond were also observed, indicating an increase in crystallinity during the drying process. These insights provide valuable information for understanding the nanocellulose structures in material processing and designing materials with advanced functionalities.
Article
Chemistry, Physical
Min Li, WenCai Lu, John ZengHui Zhang
Summary: The study successfully extended the coarse-graining strategy to ultra-coarse-grained models and effectively parameterized liquid water, accurately predicting some important properties of liquid water. Additionally, two polarizable states of UCG molecules were observed after system equilibration. The results demonstrate that the proposed UCG models can accelerate liquid water simulation effectively.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Immunology
Emily R. Rhodes, Jonathan G. Faris, Brian M. Petersen, Kayla G. Sprenger
Summary: Through molecular dynamics simulations, this study found that framework mutations can significantly alter the distribution of VH-VL interface angles, which in turn affect the local flexibility of antibodies by changing the solvent accessible surface area. These findings emphasize the limitations of static antibody crystal structures and demonstrate the dynamic nature of antibodies in solution. The study further highlights the importance of framework mutations in antibody structure and lays the foundation for establishing design principles to create antibodies with increased specificity, stability, and breadth.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Physical
Federica Lodesani, Maria Cristina Menziani, Shingo Urata, Alfonso Pedone
Summary: This study systematically investigates the effects of simulation conditions on crystallization in highly viscous systems and finds that bias factor and temperature are the most effective parameters. Moreover, temperature rescaling proves to be a reliable approach for recovering free energy surfaces at lower temperatures.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Cell Biology
Susanna Croci, Mary Anna Venneri, Stefania Mantovani, Chiara Fallerini, Elisa Benetti, Nicola Picchiotti, Federica Campolo, Francesco Imperatore, Maria Palmieri, Sergio Daga, Chiara Gabbi, Francesca Montagnani, Giada Beligni, Ticiana D. J. Farias, Miriam Lucia Carriero, Laura Di Sarno, Diana Alaverdian, Sigrid Aslaksen, Maria Vittoria Cubellis, Ottavia Spiga, Margherita Baldassarri, Francesca Fava, Paul J. Norman, Elisa Frullanti, Andrea M. Isidori, Antonio Amoroso, Francesca Mari, Simone Furini, Mario U. Mondelli, Mario Chiariello, Alessandra Renieri, Ilaria Meloni
Summary: The L412F polymorphism in TLR3 is associated with severity of COVID-19, particularly in males. Research has shown that this polymorphism affects immune system autophagy activity and reduces production of certain cytokines, while also increasing the risk of developing autoimmune diseases in COVID-19 patients.
Article
Genetics & Heredity
Stefania Mantovani, Sergio Daga, Chiara Fallerini, Margherita Baldassarri, Elisa Benetti, Nicola Picchiotti, Francesca Fava, Anna Galli, Silvia Zibellini, Mirella Bruttini, Maria Palmieri, Susanna Croci, Sara Amitrano, Diana Alaverdian, Katia Capitani, Simone Furini, Francesca Mari, Ilaria Meloni, Elisa Frullanti, Mario U. Mondelli, Alessandra Renieri
Summary: TLR7 variants in male patients lead to impaired immune response to viruses like SARS-CoV-2, resulting in severe COVID-19. These variants cause significant damage to the TLR7 signaling pathway and hinder the type I and II interferon responses.
GENES AND IMMUNITY
(2022)
Article
Genetics & Heredity
Chiara Fallerini, Nicola Picchiotti, Margherita Baldassarri, Kristina Zguro, Sergio Daga, Francesca Fava, Elisa Benetti, Sara Amitrano, Mirella Bruttini, Maria Palmieril, Susanna Croci, Mirjam Lista, Giada Beligni, Floriana Valentino, Ilaria Meloni, Marco Tanfoni, Francesca Minnai, Francesca Colombo, Enrico Cabri, Maddalena Fratelli, Chiara Gabbi, Stefania Mantovani, Elisa Frullanti, Marco Gori, Francis P. Crawley, Guillaume Butler-Laporte, Brent Richards, Hugo Zeberg, Miklos Lipcsey, Michael Hultstrom, Kerstin U. Ludwig, Eva C. Schulte, Erola Pairo-Castineira, John Kenneth Baillie, Axel Schmidt, Robert Frithiof, Francesca Mari, Alessandra Renieri, Simone Furini
Summary: The study developed a machine-learning model using common and rare exonic variants to predict COVID-19 severity. By selecting key Boolean features and combining them into an Integrated PolyGenic Score, the model offers insights into the genetic contribution to disease severity. A quarter of the selected genes are sex-specific, and pathway analysis highlighted the multi-organ nature of COVID-19 severity. This model could potentially aid in diagnostics, therapeutics, and disease management at the bedside.
Review
Biochemistry & Molecular Biology
Kristina Zguro, Chiara Fallerini, Francesca Fava, Simone Furini, Alessandra Renieri
Summary: The COVID-19 pandemic has had a significant impact on global public health, societies, and economies. Understanding the disease better is crucial, and international collaborations have identified genetic markers that explain the varied clinical outcomes and can guide the development of diagnostics and therapeutics.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Chemistry, Medicinal
Carmen Domene, Leonardo Darre, Victoria Oakes, Saul Gonzalez-Resines
Summary: This study investigated the pathway of capsaicin entering TRP ion channels and identified two possible binding modes. The findings contribute to a better understanding of TRPV channels and provide guidance for the design of selective inhibitors, potentially leading to novel pharmacological applications targeting the TRPV1 channel.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(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)
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)