Article
Biochemistry & Molecular Biology
Shahid Parwez, Pinaki Parsad Mahapatra, Shakil Ahmed, Mohammad Imran Siddiqi
Summary: A deep neural network-based workflow was proposed for the virtual screening of compounds targeting TACE proteins. Three compounds showed significant inhibition and stable interaction potential against TACE protein, making them potential candidates for further development as novel inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Pharmacology & Pharmacy
Gaia Pasqualetto, Marika Zuanon, Andrea Brancale, Mark T. Young
Summary: The ATP-gated ion channels P2X4 and P2X7 receptors are drug targets for inflammatory pain. Through virtual screening, a compound (GP-25) was found to display antagonist activity at human P2X7 but not at human P2X4. Further screening led to the discovery of five additional compounds with antagonist activity at human P2X7. Docking experiments revealed the structural basis for the lack of activity of GP-25 at human P2X4.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kavita Kumari Kakarala, Kaiser Jamil
Summary: Key drug targets in various cancers such as NSCLC, bladder cancer, pancreatic cancer, CML, ALL, and colorectal cancer include EGFR1, VEGFR2, Bcr-Abl, and Src kinases. The limited efficacy of available drugs targeting these kinases is due to drug resistance and toxicity, prompting the need for alternative allosteric drugs. This study successfully applied drug repurposing and computational methods to identify potential kinase inhibitors targeting novel allosteric sites on protein structures, with peptides identified as promising inhibitors for therapy. New druggable allosteric sites for kinase-specific drug discovery have also been identified for future research.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Alfredo Rus, Victor M. Bolanos-Garcia, Agatha Bastida, Paula Morales
Summary: This study utilizes virtual screening and molecular docking to identify potential HPSE inhibitors that may have therapeutic potential in treating chronic and infectious diseases.
Article
Biochemistry & Molecular Biology
Yunshuo Zhao, Xiaotong Chen, Sifan Lyu, Zhe Ding, Yahong Wu, Yanfeng Gao, Jiangfeng Du
Summary: Overactivation of P2X7 receptors promotes tumor growth and invasion, and inhibiting its activation may be a potentially effective anti-tumor therapy strategy. This study identified several novel P2X7R antagonists through a combination of homology modeling and other methods, which effectively prevented P2X7R pore opening and could be further explored for their anti-cancer activity.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Chemistry, Multidisciplinary
Shahzaib Ahamad, Kanipakam Hema, Dinesh Gupta
Summary: This study focuses on the screening of two chemical libraries to find TTBK2 inhibitors. Four active compounds were shortlisted and found to stabilize the TTBK2 protein. This study provides valuable insights into the structural changes and could aid in the development of novel TTBK2 inhibitors.
Article
Biochemistry & Molecular Biology
Ravi Kant, Prakash Jha, Daman Saluja, Madhu Chopra
Summary: This study investigated the structural and functional relationship between Ng-MurI and D-glutamate in Neisseria gonorrhoeae. Through homology modeling, molecular docking, and molecular dynamics simulations, novel compounds with potential inhibitory activity against Ng-MurI were identified. These findings provide insights for the design and development of Ng-MurI inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Applied
Weidan Guo, Yu Xiao, Xiangjin Fu, Zhao Long, Yue Wu, Qinlu Lin, Kangzi Ren, Liwen Jiang
Summary: In this study, the effect of Douchi extract (DWE) on a-glucosidase and angiotensin-converting enzymes (ACE) was investigated. Peptidomics approach based on UPLC-MS/MS was used to identify several novel peptides with inhibitory activity against a-glucosidase and ACE. The results showed that DWE had high inhibition rates on a-glucosidase and moderate inhibition rates on ACE. Through peptidomics and molecular docking, new peptides with potential inhibitory activity against a-glucosidase and ACE were discovered.
Article
Multidisciplinary Sciences
Navanath Kumbhar, Snehal Nimal, Sagar Barale, Subodh Kamble, Rohit Bavi, Kailas Sonawane, Rajesh Gacche
Summary: In this study, potent and selective inhibitors against HDAC3 were designed using ligand-based pharmacophore modeling, virtual screening, molecular docking, and MD simulations. These screened hit compounds may act as effective therapeutic agents for the treatment of cancers and neurodegenerative disorders.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Mohammad M. Al-Sanea, Garri Chilingaryan, Narek Abelyan, Grigor Arakelov, Harutyun Sahakyan, Vahram G. Arakelov, Karen Nazaryan, Shaimaa Hussein, Gharam M. Alazmi, Haifa E. Alsharari, Waad M. Al-faraj, Faten S. Alruwaili, Nouf Q. Albilasi, Tahani S. Alsharari, Abdulaziz A. S. Alsaleh, Turki M. Alazmi, Atiah H. Almalki, Nasser H. Alotaibi, Mohamed A. Abdelgawad
Summary: The human carbonic anhydrase XII (hCA XII) isozyme is a valuable pharmacological target and biomarker for cancer. Traditional hCA inhibitors lack selectivity and can cause allergies, driving the need for novel non-classical hCA XII inhibitors. This study identified potential non-classical hCA XII inhibitors using computational drug design approaches.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Faten Ahmad Alsulaimany, Haifa Almukadi, Nidal M. Omer Zabermawi, Thamer Abdulhamid Aljuhani, Omran M. Rashidi, Walaa F. Albaqami, Anwar A. Alghamdi, Aftab Ahmad, Noor Ahmad Shaik, Babajan Banaganapalli
Summary: The study identified three promising anti-TB compounds through high throughput computational screening. Further analysis showed that Irinotecan exhibited the best binding affinity and stability in forming molecular complexes with LeuRS protein, comparable to the reference inhibitor GSK656. The study also found a correlation in pharmacokinetic properties between Irinotecan and GSK656. These findings provide a basis for further experimental confirmation of Irinotecan as a potential drug for combating drug-resistant tuberculosis.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Huimin Zhang, Jindi Huang, Rui Chen, Hanxuan Cai, Yihao Chen, Shuyun He, Jianrong Xu, Jiquan Zhang, Ling Wang
Summary: The study utilized machine learning and deep learning methods to construct multiple predictive models, with the findings showing that the FP-GNN model performed best in predicting CDK9 inhibitors. This led to the discovery of new CDK9 inhibitors compounds, which exhibited strong anticancer activity in various cancer cell lines.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Janak Sunuwar, Rajeev K. Azad
Summary: Antimicrobial resistance poses a threat to global healthcare systems, but machine learning offers potential in uncovering novel resistance genes and aiding the development of more effective solutions.
Article
Chemistry, Multidisciplinary
Ritu Jakhar, Alka Khichi, Dev Kumar, Mehak Dangi, Anil Kumar Chhillar
Summary: This study utilized a QSAR modeling-based virtual screening approach to identify potential inhibitors of DNA gyrase. The identified inhibitors were further validated through docking and molecular dynamics simulations.
Article
Chemistry, Medicinal
Ilenia Giangreco, Abhik Mukhopadhyay, Jason C. Cole
Summary: This study discusses the results of a validation study of a ligand-based screening method, which can use multiple flexible ligands overlaid as a query simultaneously, thus improving virtual screening performance.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Editorial Material
Biochemistry & Molecular Biology
Michael D. Paul, Hayarpi Torosyan, Natalia Jura
Summary: In this study, the authors characterized the epidermal growth factor-dependent interactome of the pseudokinase PEAK3 and demonstrated its oncogenic effects. These findings provide new insights into the signaling mechanisms of PEAK3.
Article
Genetics & Heredity
Wen Xi Cao, Angelo Karaiskakis, Sichun Lin, Stephane Angers, Howard D. Lipshitz
Summary: During the maternal-to-zygotic transition, a subset of maternally supplied gene products is cleared, allowing activation of zygotic gene expression. In Drosophila embryos, the protein SMG translationally represses maternal mRNAs, and a protein named Bard is required for the degradation of SMG, thus regulating the orderly progression through the maternal-to-zygotic transition.
Article
Chemistry, Multidisciplinary
David N. Philpott, Surath Gomis, Hansen Wang, Randy Atwal, Abdellali Kelil, Tanja Sack, Brandon Morningstar, Chris Burnie, Edward H. Sargent, Stephane Angers, Sachdev Sidhu, Shana O. Kelley
Summary: The rapid on-cell phage display platform presented in this study accelerates the development of high-performance human antibodies by mimicking the complex in vivo binding environment, improving screening efficiency and accuracy.
ACS CENTRAL SCIENCE
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Shikai Hu, Sucha Singh, Minakshi Poddar, Jackson McGaughey, Levi Blazer, Jarret Adams, Sachdev Sidhu, Stephane Angers, Satdarshan Monga
Item Withdrawal
Biochemistry & Molecular Biology
S. Angers
Article
Multidisciplinary Sciences
Megan Lo, Amnon Sharir, Michael D. Paul, Hayarpi Torosyan, Christopher Agnew, Amy Li, Cynthia Neben, Pauline Marangoni, Libin Xu, David R. Raleigh, Natalia Jura, Ophir D. Klein
Summary: The protein Canopy4 has been found to regulate the level of membrane sterol lipids, and its absence in mouse embryos leads to developmental defects related to Hedgehog (Hh) signaling, particularly changes in digit number. This study reveals a previously unknown aspect of Hh pathway regulation through control of membrane composition.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ahmad N. Nabhan, Joshua D. Webster, Jarret J. Adams, Levi Blazer, Christine Everrett, Celine Eidenschenk, Alexander Arlantico, Isabel Fleming, Hans D. Brightbill, Paul J. Wolters, Zora Modrusan, Somasekar Seshagiri, Stephane Anders, Sachdev S. Sidhu, Kim Newton, Joseph R. Arron, Vishva M. Dixit
Summary: Wnt ligands control stem cell activity by oligomerizing different combinations of Fzd and Lrp5/6 receptors. In the lung alveoli, epithelial, endothelial, and stromal cells express distinct Fzd receptors. Fzd5 is specifically required for alveolar epithelial stem cell activity, while fibroblasts use different Fzd receptors. Canonical Wnt signaling in alveolar epithelial stem cells can be activated by either Fzd5 or non-canonical Fzd6, providing a potential strategy for promoting regeneration during lung injury.
Article
Chemistry, Multidisciplinary
Zongjie Wang, Hansen Wang, Sichun Lin, Mahmoud Labib, Sharif Ahmed, Jagotamoy Das, Stephane Angers, Edward H. Sargent, Shana O. Kelley
Summary: Nanoneedles are effective in delivering biomolecules to cells, but the mechanisms underlying cell-nanoneedle interactions are not well understood. In this study, we developed a new method to generate nanoneedles, confirmed their cargo delivery capability, and investigated the genetic factors involved in the process. Our results showed that the nanoneedles disrupted cell membranes, increased the expression of cell-cell junction proteins, and downregulated transcriptional factors of the NF kappa B pathway. This disturbance caused most cells to be trapped in the G2 phase, where endocytosis activities are highest. This system provides a new model for studying cell interactions with high-aspect-ratio materials.
Article
Biochemistry & Molecular Biology
Nevraj S. Kejiou, Lena Ilan, Stefan Aigner, Enching Luo, Tori Tonn, Hakan Ozadam, Muyoung Lee, Gregory B. Cole, Ines Rabano, Nishani Rajakulendran, Brian A. Yee, Hamed S. Najafabadi, Trevor F. Moraes, Stephane Angers, Gene W. Yeo, Can Cenik, Alexander F. Palazzo
Summary: In this study, the researchers investigated the factors that regulate compartment specific mRNA translation in human cells. They found that the glycolytic enzyme Pyruvate Kinase M (PKM) interacts with polysomes and influences mRNA translation, and this interaction is regulated by ADP levels. Further experiments indicated that PKM binds to mRNA sequences downstream of lysine- and glutamate-enriched tracts and causes translational stalling near these sequences. The recruitment of PKM to polysomes depends on poly-ADP ribosylation activity, suggesting a link between cellular metabolism and mRNA translation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Hayarpi Torosyan, Michael D. Paul, Antoine Forget, Megan Lo, Devan Diwanji, Krzysztof Pawlowski, Nevan J. Krogan, Natalia Jura, Kliment A. Verba
Summary: In this study, the cryo-EM structure of the PEAK3/14-3-3 complex was presented, revealing the asymmetric binding mode and the unique secondary interaction between PEAK3 and 14-3-3. It was also found that PKD regulates the binding of PEAK3 and 14-3-3, and disruption of this binding leads to nuclear enrichment of PEAK3 and distinct protein-protein interactions. The results demonstrate how 14-3-3 modulates PEAK3 localization and protein-protein interactions.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Xian Wang, Zheyuan Gong, Tiancong Wang, Junhui Law, Xin Chen, Siyi Wanggou, Jintian Wang, Binbin Ying, Michelle Francisco, Weifan Dong, Yi Xiong, Jerry J. Fan, Graham MacLeod, Stephane Angers, Xuejun Li, Peter B. Dirks, Xinyu Liu, Xi Huang, Yu Sun
Summary: Researchers have developed a mechanical approach using magnetic carbon nanotubes to treat chemoresistant glioblastoma (GBM). GBM cells can internalize the nanotubes and their mobilization by rotating magnetic fields leads to cell death. In vivo studies show that spatiotemporally controlled release of the nanotubes inhibits GBM growth. Functionalizing the nanotubes with an antibody that recognizes GBM cell surface antigen CD44 enhances their recognition of cancer cells and improves therapeutic efficacy. This study establishes the use of magnetic carbon nanotubes as a treatment option for GBM.
Article
Radiology, Nuclear Medicine & Medical Imaging
Amanda J. Boyle, Zhongli Cai, Siobhan O'Brien, Jennifer Crick, Stephane Angers, Raymond M. Reilly
Summary: This study aimed to compare the radiobiological effectiveness of [64Cu]Cu-NOTA-panitumumab F(ab')2 and [177Lu]Lu-NOTA-panitumumab F(ab')2 radioimmunotherapy (RIT) agents with XRT in decreasing the clonogenic survival fraction (SF) of EGFR-positive human PDAC cell lines. The results showed that both RIT agents were less effective than XRT in reducing the SF of PDAC cells.
NUCLEAR MEDICINE AND BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Lingling Zhang, Md. Abedin, Ha-Neul Jo, Jacklyn Levey, Quynh Chau Dinh, Zhe Chen, Stephane Angers, Harald J. Junge
Summary: Norrin (NDP) and WNT7A/B stimulate the FZD4-LRP5/6 complex to induce beta-catenin-dependent signaling in endothelial cells (ECs), thus maintaining the blood-brain and blood-retina barrier (BBB, BRB). A tetravalent antibody modality, F4L5.13, was found to have agonist activities in Tspan12-/- mice, leading to the alleviation of BRB defects, retinal hypovascularization, and restoration of neural function. Administration of F4L5.13 rapidly and substantially restores the BRB in a genetic model of impaired maintenance.
Article
Biochemistry & Molecular Biology
Tanja Sack, Piriththiv Dhavarasa, Daniel Szames, Siobhan O'Brien, Stephane Angers, Shana O. Kelley
Summary: Comparing to nuclear DNA repair mechanisms, the characterization of mtDNA repair mechanisms is difficult due to the challenge of specifically addressing mitochondrial damage. This study uses an mtDNA-damaging agent in combination with CRISPR/Cas9 screening to identify genes essential for mtDNA damage response and confirms the responsiveness of WRNIP1 to mtDNA damage for the first time. The study also reveals the mitochondrial role of WRNIP1 in innate immune signaling and nuclear genome maintenance.
ACS CHEMICAL BIOLOGY
(2023)
Article
Cell Biology
Shikai Hu, Silvia Liu, Yu Bian, Minakshi Poddar, Sucha Singh, Catherine Cao, Jackson McGaughey, Aaron Bell, Levi L. Blazer, Jarret J. Adams, Sachdev S. Sidhu, Stephane Angers, Satdarshan P. Monga
Summary: Using single-cell analysis, the study found that Wnt2 and Wnt9b are expressed in endothelial cells in the liver and play important roles in liver zonation and regeneration. Knocking out Wnt2 and Wnt9b resulted in the loss of 0-catenin targets and re-expression of zone 1 genes in zone 3, indicating the dynamicity of the liver zonation process. Activation of Wnt signaling rescued liver zonation and regeneration, and also promoted regeneration in acetaminophen overdose acute liver failure.
CELL REPORTS MEDICINE
(2022)