Article
Biochemistry & Molecular Biology
Sang Hyun Lim, Jamie Snider, Liron Birimberg-Schwartz, Wan Ip, Joana C. Serralha, Hugo M. Botelho, Miqueias Lopes-Pacheco, Madalena C. Pinto, Mohamed Taha Moutaoufik, Mara Zilocchi, Onofrio Laselva, Mohsen Esmaeili, Max Kotlyar, Anna Lyakisheva, Priscilla Tang, Lucia Lopez Vazquez, Indira Akula, Farzaneh Aboualizadeh, Victoria Wong, Ingrid Grozavu, Teuta Opacak-Bernardi, Zhong Yao, Meg Mendoza, Mohan Babu, Igor Jurisica, Tanja Gonska, Christine E. Bear, Margarida D. Amaral, Igor Stagljar
Summary: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel that plays a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. This study used a high-throughput screening technique to map the protein-protein interactions of CFTR and identify potential drug targets for CF treatment. They discovered candidate proteins, such as FGL2, that may have significant effects on CFTR function in CF pathophysiology.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Chemistry, Medicinal
Yiwei Zhang, Jiabei Guo, Jiongjia Cheng, Zhenghua Zhang, Fenghua Kang, Xiaoxing Wu, Qian Chu
Summary: Therapeutic peptides have revolutionized treatment for many human diseases. In recent decades, stapled helical peptides have made rapid progress in drug discovery. Compared to unstabilized linear peptides, stapled helical peptides have shown superior binding affinity, selectivity, membrane permeability, and metabolic stability, offering exciting potential for targeting challenging protein-protein interfaces. This Perspective summarizes the recent use of high-throughput screening technologies for identifying potent stapled helical peptides with optimized binding properties, aiming to accelerate the development of stapled helical peptides as the next generation of therapeutic peptides for various human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Anil K. Giri, Aleksander Ianevski
Summary: The interactions between leukemic blasts and cells within the bone marrow environment play a crucial role in oncogenesis, cancer stem cell survival, and drug resistance in hematological cancers. Recent advancements in drug screening technologies and computational algorithms are helping to target previously undruggable proteins and complex pathways, particularly in the context of leukemic cell-bone microenvironment interactions.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Physical
Matthew Bain, Jose L. Godinez Castellanos, Stephen E. Bradforth
Summary: High-repetition-rate lasers have the potential to revolutionize ultrafast spectroscopy by enabling routine analysis for machine learning models in the design of photochemical syntheses. In this study, we combine innovations in line scan cameras and micro-electro-mechanical grating modulators with high-pressure liquid chromatography pumps to develop a transient absorption spectrometer that can characterize photoreactions in minutes. Additionally, we demonstrate the utility of this technique in exploring the effects of conformational modification on excited-state processes.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Biotechnology & Applied Microbiology
Ismail S. Mohiuddin, Sung-Jen Wei, In-Hyoung Yang, Gloria M. Martinez, Shengping Yang, Eun J. Cho, Kevin N. Dalby, Min H. Kang
Summary: A novel cell-based luminescence assay was developed to identify inhibitors targeting c-MYC transcriptional activation, leading to the discovery of five potential lead compounds with significant ability to kill cancer cells. Two candidate compounds from the DNA-PKcs assay and three from the MK2 assay were identified through a two-step validation method.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Pharmacology & Pharmacy
Christin Pohl, Sujata Mahapatra, Alina Kulakova, Werner Streicher, Gunther H. J. Peters, Allan Norgaard, Pernille Harris
Summary: This study applies small angle X-ray scattering (SAXS), which is not typically used in industrial protein screening, in a high throughput screening workflow to address problems of contradicting results and reproducibility among different methods. The results demonstrate that SAXS can provide valuable information on interparticle interactions, even without time-consuming modeling, and can be used as a tool for in-depth knowledge highly useful for protein formulation development.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Priyanka Parijat, Saraswathi Ponnam, Seetharamaiah Attili, Kenneth S. Campbell, Mohammed El-Mezgueldi, Mark Pfuhl, Thomas Kampourakis
Summary: The unmet demand for new heart failure therapeutics is well recognized and targeting the contractile myofilaments has shown potential for the development of new drugs. However, limited clinical use and incomplete understanding of myofilament function have hindered progress in this area. In this study, new high throughput screening platforms were designed and validated to explore the effects of small molecule effectors on the interactions between cardiac troponin C and troponin I subunits. The results suggest that sarcomeric protein-directed screening platforms are suitable for developing compounds that modulate cardiac myofilament function.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Zhenzhen Wang, Jiangjiexing Wu, Jia-Jia Zheng, Xiaomei Shen, Liang Yan, Hui Wei, Xingfa Gao, Yuliang Zhao
Summary: The study uses density functional theory calculations to investigate the principles behind the SOD-like catalytic activity of nanomaterials, proposing energy level and adsorption energy principles for quantitatively describing the activity. These principles were validated through experiments on metal-organic frameworks and can be easily implemented in computer programs for screening NMs with intrinsic SOD-like activity. A general predicting theory for superoxide-dismutase mimicking nanomaterials is currently lacking.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Taj Mohammad, Yash Mathur, Md Imtaiyaz Hassan
Summary: InstaDock is a free and open access GUI program that efficiently performs molecular docking and high-throughput virtual screening. It is the easiest and more interactive interface for molecular docking and high-throughput virtual screening compared to existing GUIs.
BRIEFINGS IN BIOINFORMATICS
(2021)
Review
Biochemistry & Molecular Biology
Agni F. M. Gavriilidou, Kleitos Sokratous, Hsin-Yung Yen, Luigi De Colibus
Summary: Studying protein-ligand interactions can greatly assist in the design of new therapeutic molecules. Various techniques used in drug discovery, such as isothermal titration calorimetry and nuclear magnetic resonance spectroscopy, rely on protein crystallography and cryo-electron microscopy. Native mass spectrometry is a versatile method for studying proteins and their interactions, providing valuable insights into protein structure and thermodynamics.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Physical
Vei Wang, Gang Tang, Ya-Chao Liu, Ren-Tao Wang, Hiroshi Mizuseki, Yoshiyuki Kawazoe, Jun Nara, Wen Tong Geng
Summary: Two-dimensional materials have attracted attention for their unique physical properties and their ability to meet the demands of nanoscale devices. In this study, we conducted high-throughput calculations and screening to identify 73 direct-gap and 183 indirect-gap 2D nonmagnetic semiconductors based on criteria for thermodynamic, mechanical, dynamic, and thermal stabilities, as well as conductivity type. A database of these materials was created, providing a platform for computational modeling and design of new 2D semiconductors and heterostructures in applications such as photocatalysis and nanoscale devices. Additionally, a linear fitting model was proposed to accurately evaluate band gap, ionization energy, and electron affinity of 2D semiconductors with lower computational cost compared to hybrid DFT methods.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Physical
Mads Kruse, Urko Petralanda, Morten N. Gjerding, Karsten W. Jacobsen, Kristian S. Thygesen, Thomas Olsen
Summary: We performed a high throughput computational search in the C2DB and identified 63 ferroelectric materials, including 49 with in-plane polarization, 8 with out-of-plane polarization, and 6 with coupled in-plane and out-of-plane polarization. Most known 2D ferroelectrics were recovered and the predicted ones are accessible by direct exfoliation. About 25% of the materials showed a metastable state in the non-polar structure. We also discussed the case of VAgP2Se6, a magnetic pyroelectric material with switchable polarization coupled to magnetic excitation spectrum.
NPJ COMPUTATIONAL MATERIALS
(2023)
Article
Multidisciplinary Sciences
Shengya Cao, Sean M. Peterson, Soren Muller, Mike Reichelt, Christian McRoberts Amador, Nadia Martinez-Martin
Summary: Cell surface receptors play a critical role in cell signaling and constitute a significant portion of human genes. A new method based on extracellular vesicles has been developed to detect receptor-ligand interactions in membranes, showcasing broad applicability and enhanced detection capability. This platform bypasses the need for membrane protein purification and allows for characterization of interactomes for any cell surface-expressed target in its native state.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Alexander Neumann, Isaac Attah, Haneen Al-Hroub, Vigneshwaran Namasivayam, Christa E. Mueller
Summary: The human ATP- and UTP-activated P2Y2 receptor plays a role in various pathological conditions. However, the current P2Y2 receptor antagonists have limitations. In this study, researchers utilized virtual screening and molecular docking to discover novel antagonist scaffolds for the P2Y2 receptor. The identified compounds showed similar binding modes with a known potent orthosteric antagonist. This study provides a basis for the development of future drug candidates for the P2Y2 receptor.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Multidisciplinary
Yifeng Tang, Jeremiah Y. Kim, Carman K. M. Ip, Azadeh Bahmani, Qing Chen, Matthew G. Rosenberger, Aaron P. Esser-Kahn, Andrew L. Ferguson
Summary: A machine learning-enabled active learning pipeline was developed to guide the screening and discovery of small molecule immunomodulators that can improve immune responses. By using high throughput screening and data-driven predictive models, novel small molecules with enhanced or suppressed innate immune signaling capacity were discovered, and chemical design rules were extracted.
Article
Biochemical Research Methods
K. Ramki, G. Thiruppathi, Selva Kumar Ramasamy, P. Sundararaj, P. Sakthivel
Summary: A chromone-based ratiometric fluorescent probe L2 was developed for the selective detection of Hg(II) in a semiaqueous solution. The probe exhibited enhanced fluorescence in its aggregated state and even higher fluorescence when chelated with Hg(II). The probe demonstrated high sensitivity and specificity for Hg(II) detection and was successfully applied for imaging Hg(II) in a living model.
Article
Biochemical Research Methods
Qun Zhang, Rui Yang, Gang Liu, Shiyan Jiang, Jiarui Wang, Juqiang Lin, Tingyin Wang, Jing Wang, Zufang Huang
Summary: This research aims to develop a cost-effective and portable method for measuring creatinine levels using the enhanced Tyndall effect phenomenon. The method offers a promising solution for monitoring renal healthcare in resource-limited settings.
