Article
Biochemistry & Molecular Biology
Anna Scarsi, Marco Ponassi, Chiara Brullo, Camillo Rosano, Andrea Spallarossa
Summary: Imidazolidine-2-thione is a promising chemical scaffold with pharmaceutical potential, and can be used to synthesize antimicrobial, anticancer, and pesticide agents. The formation of mono-acylated or di-acylated thiourea derivatives depends on the nature of the acyl chloride reagent used. Computational simulations helped explain the factors influencing the outcome of the reaction. The synthesized compounds showed no cytotoxicity on cancer cell lines and exhibited good pharmacokinetics properties and drug-like characteristics.
MOLECULAR DIVERSITY
(2023)
Article
Chemistry, Physical
Alessandra Marega Motta, Maressa Donato, Giovanna Mobbili, Paolo Mariani, Rosangela Itri, Francesco Spinozzi
Summary: This study investigates the mechanisms of interaction between Rhamnolipids (RLs) and simulated plasma membrane models. The results show that mono-RL primarily interacts with the outer leaflet of the membrane through insertion without pore formation, but induces lipid mixing. On the other hand, di-RLs initially interact through insertion and later undergo pore formation.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Engineering, Chemical
Qingbo Huang, Song Liu, Yanan Guo, Gongping Liu, Wanqin Jin
Summary: In this study, a graphene oxide (GO) membrane with charged interlayer channels was developed for the separation of mono-/di-valent ions. The membrane achieved selective transport of monovalent ions by utilizing size-sieving and electrostatic repulsion. The introduction of polyethyleneimine (PEI) into the interlayer channels not only controlled the charge property but also increased the hydrophilicity of the membrane surface. The optimal GO-PEI membrane exhibited high permeation rates and selectivity for monovalent ions.
JOURNAL OF MEMBRANE SCIENCE
(2022)
Article
Engineering, Chemical
Xiuxiu Ren, Shengjie Yang, Rong Xu, Meng Guo, Weiqiu Huang, Ming Ding, Jing Zhong
Summary: By exchanging Na+ with mono- and divalent cations, the structure and performance of Na-mordenite zeolite membranes were modified, resulting in higher water capacity and improved separation efficiency in the dehydration of acetic acid by pervaporation.
JOURNAL OF MEMBRANE SCIENCE
(2022)
Article
Food Science & Technology
Paulina Strugala-Danak, Maciej Spiegel, Kacper Hurynowicz, Janina Gabrielska
Summary: Malvidin and its derivatives exhibit strong antioxidative and antiradical properties, acting through hydrogen atom transfer from the C3-hydroxyl and increasing packing order in the hydrophilic region of membrane bilayers. The combination of molecular dynamics and quantum mechanics helps explain the fluctuating charge distribution among the investigated species, shedding light on the potential pharmacological applications of malvidins.
JOURNAL OF FUNCTIONAL FOODS
(2022)
Article
Polymer Science
Huiying Liao, Yunlong Tan, Ke Zhang, Guyu Xiao
Summary: The microstructure and properties of proton exchange membranes (PEMs) can be improved by adjusting the distribution modes of sulfonic acid groups. Different structures of sulfonated poly(arylene ether phosphine oxide)s (sPAEPO) with varying degrees of sulfonation were synthesized and it was found that the distribution modes of the sulfonic acid groups and the structural unit of diphenol monomer greatly affected the properties of the resulting PEMs. By adjusting the sulfonation degree, the comprehensive properties of the PEMs can be further improved.
Article
Engineering, Chemical
Suwattana Pruksasri, Theresa Schwabl, Senad Novalin
Summary: The study found that the selectivity values for separating fructose, glucose, sucrose, polyphenols, malic acid, and minerals in apple juice vary, as do the losses. The highest selectivity occurs when the rejection for the larger compound is close to unity.
CHEMICAL ENGINEERING SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Candy Laura Steffen, Pelin Kaya, Elisabeth Schaffner-Reckinger, Daniel Abankwa
Summary: RAS drug development has made significant progress, and new approaches to target this feared oncogene have emerged. The lessons learned from developing covalent and non-covalent inhibitors and the potential of macromolecular binders are discussed. The future may involve the development of non-covalent inhibitors derived from covalent binders and the use of reversible small molecule binders for novel targeting modalities. The importance of creative ideas in exterminating RAS in cancer and other RAS pathway-driven diseases is emphasized.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Chemistry, Physical
Zirui Zhang, Clarisse G. Ricci, Chao Fan, Li-Tien Cheng, Bo Li, J. Andrew McCammon
Summary: The hybrid approach combines the Monte Carlo method, a variational implicit-solvent model (VISM), and a binary level-set method for simulating biomolecular binding in an aqueous solvent. It estimates the solvation free energy for the biomolecular complex by minimizing the VISM free-energy functional, accurately predicting the electrostatic part of the solvation free energy by shifting the dielectric boundary. The new and fast binary level-set method allows for this functional minimization in each MC move.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Chemistry, Medicinal
Terra Sztain, Rommie Amaro, J. Andrew McCammon
Summary: By using Gaussian accelerated molecular dynamics, this study identified cryptic pockets within the SARS-CoV-2 main protease, revealing druggable conformational states far from the active site. The simulations demonstrated comparable dynamics and pocket volumes to conventional brute force simulations conducted on significantly longer timescales.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Multidisciplinary Sciences
Hamidreza Rahmani, Wen Ma, Zhongjun Hu, Nadia Daneshparvar, Dianne W. Taylor, J. Andrew McCammon, Thomas C. Irving, Robert J. Edwards, Kenneth A. Taylor
Summary: The atomic structure of myosin tail in thick filaments isolated from Lethocerus indicus flight muscle is asymmetric, with differences in skip regions and nonhelical C termini. The study provides insights into the uncoiling of coiled-coils at the head-tail junction and sheds light on the complex roles of thick filaments in muscle contraction across species.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Terra Sztain, Thomas G. Bartholow, D. John Lee, Lorenzo Casalino, Andrew Mitchell, Megan A. Young, Jianing Wang, J. Andrew McCammon, Michael D. Burkart
Summary: Enzymes in metabolic pathways utilize a variety of regulatory mechanisms to maintain homeostasis, with carrier proteins playing an essential role in substrate shuttling. A unique communication mechanism between ACP and partner enzymes has been demonstrated, showing allosteric regulation dependent on fatty acid chain length. These findings provide insights into cargo communication by ACP and can potentially be used for engineering carrier protein-dependent pathways for specific products.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Physical
Surl-Hee Ahn, Sanbo Qin, Jason Z. Zhang, J. Andrew McCammon, Jin Zhang, Huan-Xiang Zhou
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Chemistry, Multidisciplinary
Terra Sztain, Surl-Hee Ahn, Anthony T. Bogetti, Lorenzo Casalino, Jory A. Goldsmith, Evan Seitz, Ryan S. McCool, Fiona L. Kearns, Francisco Acosta-Reyes, Suvrajit Maji, Ghoncheh Mashayekhi, J. Andrew McCammon, Abbas Ourmazd, Joachim Frank, Jason S. McLellan, Lillian T. Chong, Rommie E. Amaro
Summary: Through simulations, the study reveals the mechanism of spike protein receptor binding domain (RBD) opening in SARS-CoV-2 infection, highlighting the crucial role of N-glycan in facilitating RBD opening. This research represents a milestone in ensemble pathway simulations and provides a foundation for understanding the fundamental mechanisms of viral entry and infection.
Article
Multidisciplinary Sciences
Varnavas D. Mouchlis, Daiki Hayashi, Alexis M. Vasquez, Jian Cao, J. Andrew McCammon, Edward A. Dennis
Summary: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) associates with lipoproteins in human plasma and hydrolyzes oxidized phospholipids. The mechanism of enzyme-membrane association and substrate specificity were studied using lipidomics and mass spectrometry techniques.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Thomas G. Laughlin, Amar Deep, Amy M. Prichard, Christian Seitz, Yajie Gu, Eray Enustun, Sergey Suslov, Kanika Khanna, Erica A. Birkholz, Emily Armbruster, J. Andrew McCammon, Rommie E. Amaro, Joe Pogliano, Kevin D. Corbett, Elizabeth Villa
Summary: This study identifies a protein called ChmA as the main component of the bacteriophage nuclear shell. The structure and dynamics of the ChmA shell provide insights into its formation and functions.
Article
Biochemistry & Molecular Biology
Surl-Hee Ahn, Gary A. Huber, J. Andrew McCammon
Summary: Intrinsically disordered proteins (IDPs) have attracted significant attention due to their involvement in biological processes and diseases. Computational studies using Brownian dynamics (BD) simulations with a coarse-grained force field for proteins (COFFDROP) have been conducted to complement experimental work. The researchers found that IDPs' properties, such as hydrodynamic radii and entanglement indices, are influenced by salt concentration.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Joshua C. Corpuz, Ashay Patel, Tony D. Davis, Larissa M. Podust, J. Andrew McCammon, Michael D. Burkart
Summary: This study reveals the binding specificities between peptidyl carrier proteins (PCPs) and adenylation (A) domains in non-ribosomal peptide synthetases (NRPSs) using chemical biology approaches. The research also demonstrates the possibility of controlling PCP binding specificity through modifying interfacial interactions.
ACS CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yohei Takahashi, Krystal C. Bosmans, Po -Kai Hsu, Karnelia Paul, Christian Seitz, Chung-Yueh Yeh, Yuh-Shuh Wang, Dmitry Yarmolinsky, Maija Sierla, Triin Vahisalu, J. Andrew McCammon, Jaakko Kangasjaervi, Li Zhang, Hannes Kollist, Thien Trac, Julian I. Schroeder
Summary: The rise in atmospheric CO2 concentration affects stomatal closing in plants, impacting transpirational water loss, photosynthesis, and growth. This study identifies MPK4/12 and HT1 as the primary CO2 sensors in plants, located upstream of the CBC1 kinase. These findings are significant for understanding the plant response to CO2.
Article
Biochemistry & Molecular Biology
Jui-Hung Weng, Wen Ma, Jian Wu, Pallavi Kaila Sharma, Steve Silletti, J. Andrew McCammon, Susan Taylor
Summary: Mutations in LRRK2 increase the risk of Parkinson's disease, and its pathological functions are often associated with abnormal kinase activity. This study combines enhanced sampling simulations with HDX-MS to investigate the dynamic changes and allosteric communications within the C-terminal domains of LRRK2. It is found that different types of kinase inhibitors stabilize distinct kinase conformations and modulate the interdomain interactions between the kinase and GTPase domains.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Terra Sztain, Joshua C. Corpuz, Thomas G. Bartholow, Javier O. Sanlley Hernandez, Ziran Jiang, Desirae A. Mellor, Graham W. Heberlig, James J. La Clair, J. Andrew Mccammon, Michael D. Burkart
Summary: Carrier-protein-dependent metabolic pathways rely on protein-protein interactions to control enzyme reactivity and timing. Computational methods, such as the improved Rosetta score function, can be used to design customized pathways by optimizing protein-protein interactions. This method provides a promising platform for engineering carrier-protein-dependent pathways.
ACS CHEMICAL BIOLOGY
(2023)
Article
Physics, Applied
Marcus T. Hock, Abigail E. Teitgen, Kimberly J. McCabe, Sophia P. Hirakis, Gary A. Huber, Michael Regnier, Rommie E. Amaro, J. Andrew McCammon, Andrew D. McCulloch
Summary: dATP, a natural analog of ATP, has been shown to enhance cardiac function. In this study, computational modeling was used to investigate the mechanism by which dATP accelerates calcium re-uptake into the sarcoplasmic reticulum during cardiac relaxation. The results showed that dATP interacts with SERCA and increases calcium association rate constants, ultimately leading to accelerated calcium transient decay observed experimentally.
JOURNAL OF APPLIED PHYSICS
(2023)
Article
Chemistry, Physical
Christian Seitz, Ilker Deveci, J. Andrew McCammon
Summary: This study investigates how protein glycosylation and lateral crowding effects modulate the stability and dynamics of influenza neuraminidase. The results show that glycans stabilize the protein structure, while a crowded membrane environment encourages large-scale conformational changes.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)