Article
Pharmacology & Pharmacy
Men Thi Hoai Duong, Hee-Chul Ahn
Summary: This study utilized virtual fragment screening, STD NMR, in vitro kinase assay, and X-ray crystallography to identify 27 initial hits targeting JNK3 and demonstrating activity inhibition. The structures of JNK3 with a fragment and a potent inhibitor were determined by X-ray crystallography, revealing a common JNK3-binding feature.
Article
Nanoscience & Nanotechnology
Arjun Rana, Chen-Ting Liao, Ezio Iacocca, Ji Zou, Minh Pham, Xingyuan Lu, Emma-Elizabeth Cating Subramanian, Yuan Hung Lo, Sinead A. Ryan, Charles S. Bevis, Robert M. M. Karl Jr, Andrew J. Glaid, Jeffrey Rable, Pratibha Mahale, Joel Hirst, Thomas Ostler, William Liu, Colum M. O'Leary, Young-Sang Yu, Karen Bustillo, Hendrik Ohldag, David A. Shapiro, Sadegh Yazdi, Thomas E. Mallouk, Stanley J. Osher, Henry C. Kapteyn, Vincent H. Crespi, John V. Badding, Yaroslav Tserkovnyak, Margaret M. Murnane, Jianwei Miao
Summary: The researchers successfully created 138 stable magnetic monopoles on a ferromagnetic meta-lattice and used soft X-ray vector ptycho-tomography to determine their magnetization vector and emergent magnetic field. The study found that the distances between monopole-anti-monopole pairs, monopole-monopole pairs, and anti-monopole-anti-monopole pairs were 18.3 +/- 1.6 nm, 36.1 +/- 2.4 nm, and 43.1 +/- 2.0 nm, respectively. This work demonstrates the potential of ferromagnetic meta-lattices as a platform for studying the interactions and dynamics of magnetic monopoles, and the broad application of soft X-ray vector ptycho-tomography for quantitatively imaging 3D vector fields in magnetic and anisotropic materials at the nanoscale.
NATURE NANOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Natalia Kozlyuk, Benjamin A. Gilston, Lauren E. Salay, Rocco D. Gogliotti, Plamen P. Christov, Kwangho Kim, Mohiuddin Ovee, Alex G. Waterson, Walter J. Chazin
Summary: The study demonstrates the application of a fragment-based approach in discovering new types of RAGE inhibitors that specifically target the ligand-binding surface. Screening and optimization were conducted to select constructs of the RAGE ligand-binding domain and optimize conditions for NMR-based screening and co-crystallization of RAGE with hit fragments. Crystal structures of the first linked fragment compounds confirmed the effectiveness of the fragment-based approach in discovering RAGE inhibitors.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Review
Biochemistry & Molecular Biology
Stephen J. Harwood, Christopher R. Smith, J. David Lawson, John M. Ketcham
Summary: This review focuses on recent strategies to inhibit RAS-signaling by disrupting protein-protein interactions (PPIs) associated with SOS1, RAF, PDE delta, Grb2, and RAS, in hopes to provide therapies for patients with KRAS-mutant driven cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Meredith J. Zeller, Oleg Favorov, Kelin Li, Ashok Nuthanakanti, Dina Hussein, Aureliane Michaud, Daniel A. Lafontaine, Steven Busan, Alexander Serganov, Jeffrey Aube, Kevin M. Weeks
Summary: In this study, a new technology was developed that utilizes fragment-based screening and RNA structure probing to discover small-molecule fragments that bind to a target RNA structure. Using structure-activity relationship information, a novel ligand was designed with high affinity for diverse RNA targets.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Medicinal
Dilip Narayanan, Kim T. Tran, Jakob S. Pallesen, Sara M. O. Solbak, Yuting Qin, Elina Mukminova, Martina Luchini, Kristina O. Vasilyeva, Dorleta Gonzalez Chichon, Georgia Goutsiou, Cecilie Poulsen, Nanna Haapanen, Grzegorz M. Popowicz, Michael Sattler, David Olagnier, Michael Gajhede, Anders Bach
Summary: This study utilized fluorescence polarization, thermal shift assay, and surface plasmon resonance to screen 2500 small-molecule fragments, resulting in the identification of 28 high-priority hits. The binding modes of these hits were validated through saturation transfer difference NMR, providing insights into the development of novel small-molecule Keap1-Nrf2 protein-protein interaction inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Crystallography
Rafal Dolot, Aleksandra Mikolajczyk, Barbara Nawrot
Summary: HINT1 is the oldest and most widely distributed branch of the histidine triad superfamily of proteins. It plays an important role in various biological processes and has been found in many species. This study reports the first nearly complete structure of human HINT1 protein, obtained at a resolution of 1.43 angstrom. It also reveals selective binding of L-malate ion, which was not observed before.
Article
Biochemical Research Methods
Xin Luo, Liwei Wang, Pengwei Hu, Lun Hu
Summary: This paper proposes a novel protein-protein interaction (PPI) prediction algorithm (PASNVGA) that combines sequence and network information to improve prediction accuracy. The algorithm utilizes principal component analysis to extract protein features and designs a scoring function to measure higher-order connectivity. By training a variational graph autoencoder model to learn integrated protein embeddings, the prediction task is completed using a feedforward neural network.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Charles Eldrid, Mire Zloh, Constantina Fotinou, Tamas Yelland, Lefan Yu, Filipa Mota, David L. Selwood, Snezana Djordjevic
Summary: Vascular endothelial growth factors (VEGFs) are essential regulators for blood and lymphatic vessels, interacting with neuropilins and tyrosine kinase receptors. The selectivity of neuropilins and VEGF receptors in binding to VEGF proteins affects their physiological roles. Studies have shown that conformational preferences of VEGF-derived peptides beyond the C-terminal arginine contribute to the ligand selectivity of neuropilins. These findings have implications for designing selective antagonists of neuropilin functions.
Article
Biochemistry & Molecular Biology
Takatsugu Kosugi, Masahito Ohue
Summary: The study developed a quantitative estimation index QEPPI specifically for early screening of compounds targeting protein-protein interactions, which showed better performance compared to the commonly used method QED.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Xingqing Xiao, Ryan Kilgore, Sudeep Sarma, Wenning Chu, Stefano Menegatti, Carol K. Hall
Summary: This study describes the de novo design of 9-mer peptides that bind to Fab fragments using an integrated computational and experimental approach. The designed peptides showed good affinity and high product yield, laying the groundwork for future biomanufacturing translation.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Biochemistry & Molecular Biology
Ying Yu, Junsong Guo, Zhengjun Cai, Yingchen Ju, Jun Xu, Qiong Gu, Huihao Zhou
Summary: This study utilized fragment screening and X-ray crystallography to identify new building blocks and binding mechanisms for the discovery of new GyrB inhibitors. Some chemical fragments were found to affect enzyme activity, providing new insights for the design of GyrB inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ibrahima Goudiaby, Therese E. Malliavin, Eva Mocchetti, Sandrine Mathiot, Samir Acherar, Celine Frochot, Muriel Barberi-Heyob, Benoit Guillot, Frederique Favier, Claude Didierjean, Christian Jelsch
Summary: Neuropilin 1 (NRP1), a cell-surface co-receptor, has been implicated in the development and progression of various cancers. Researchers have utilized a combination of the KDKPPR peptide, a photosensitizer, and a contrast agent to target NRP1 and treat glioblastoma. By mutating specific amino acids on the protein surface, crystallography was used to determine the structure of the mutated fragment and its complex with the KDKPPR peptide, providing insights into the electrostatic interactions involved in ligand binding. Molecular dynamics simulations further analyzed the binding and mobility of the wild-type and mutant proteins.
Article
Biochemical Research Methods
Thi Ngan Dong, Graham Brogden, Gisa Gerold, Megha Khosla
Summary: The study developed a multitask transfer learning approach using large-scale protein sequence information and interaction patterns in the human interactome to address the issue of small training datasets. Experimental results demonstrated that the model achieved competitive results in virus-human and bacteria-human protein-protein interaction prediction tasks.
BMC BIOINFORMATICS
(2021)
Review
Biochemistry & Molecular Biology
Zhi-Zheng Wang, Xing-Xing Shi, Guang-Yi Huang, Ge-Fei Hao, Guang-Fu Yang
Summary: Protein-protein interactions (PPIs) play important roles in cellular processes, but are considered 'undruggable' due to their large, flat, featureless interfaces. However, fragment-based drug discovery (FBDD) has achieved success in modulating PPIs, with over ten compounds in clinical trials. This review highlights the progress, successful cases, and future trends of FBDD in modulating PPIs, aiming to provide useful guidance for drug discovery targeting PPIs.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
