Article
Biochemistry & Molecular Biology
Amy J. Rice, Russell P. Pesavento, Jinhong Ren, Isoo Youn, Youngjin Kwon, Kassapa Ellepola, Chun-Tao Che, Michael E. Johnson, Hyun Lee
Summary: The study identified small molecule inhibitors of S. aureus DHOase through high-throughput screening and direct binding analysis, laying the foundation for further design of antimicrobial inhibitors against S. aureus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sandeep Kumar, Senthil Raja Ayyannan
Summary: This study successfully identified two potential MAO-B inhibitors using computational methods, which is significant for the treatment of diseases like Alzheimer's and Parkinson's.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Zhengfang Zhang, Quan Han, Xiongxing Mao, Jinhua Liu, Wei Wang, Dong Li, Feng Zhou, Yang Ke, Lei Xu, Liu Hu
Summary: The study focused on finding novel small-molecule inhibitors against SecA protein of Candidatus Liberibacter asiaticus, the causal agent of Huanglongbing disease. Through homologous modeling, virtual screening, and bacteriostatic experiments, 93 compounds were identified with two showing strong antimicrobial activities. Molecular dynamics simulations revealed that compound P684-3808 might be a lead compound for further development.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Biochemistry & Molecular Biology
Tony Eight Lin, Li-Chin Sung, Min-Wu Chao, Min Li, Jia-Huei Zheng, Tzu-Ying Sung, Jui-Hua Hsieh, Chia-Ron Yang, Hsueh-Yun Lee, Er-Chieh Cho, Kai-Cheng Hsu
Summary: This article reports the identification of a novel noncovalent BTK inhibitor that showed favorable inhibitory activity in solid tumor cell lines, suggesting its potential for targeting BTK malignant tumors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Jiaoyu He, Qiufu Li, Yang Liu, Tianjun Li, Chunlan Cheng, Ning Li, Yanru Cui, Yunfan Shi, Yiran Liu, Xia Wei, Xianping Ding
Summary: Cervical cancer is strongly associated with persistent infection of high-risk human papillomavirus (HPV) in women of childbearing age. The E6 oncoprotein of high-risk HPV plays a crucial role in the immortalization and carcinogenicity of infected cells by binding to the tumor suppressor protein p53. In this study, small molecule compounds were screened for their potential to inhibit the binding of E6 to p53, and compound 4 showed promising tumor suppressive potential.
ARABIAN JOURNAL OF CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hyun Lee, Isoo Youn, Robel Demissie, Tasneem M. Vaid, Chun-Tao Che, Dimitri T. Azar, Kyu-Yeon Han
Summary: Matrix metalloproteinases (MMPs) play important roles in physiological and pathological processes. In this study, a fluorescence-based enzymatic assay and surface plasmon resonance were used to identify MMP-14 inhibitors. Clioquinol and chloroxine, both containing a quinoline structure, showed selective inhibitory activity against MMP-14.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mukesh Kumar, Rajni Dubey, Prakash Kumar Shukla, Deen Dayal, Kundan Kumar Chaubey, Lung-Wen Tsai, Sanjay Kumar
Summary: The key regulators BRCA1/2 play important roles in maintaining genomic integrity, and their mutations are associated with breast and ovarian cancers. Silencing the RAD52 gene in BRCA1/2 deficient cancers has shown synthetic lethality, suggesting the involvement of RAD52 in breast cancer pathogenesis. In this study, a screening of 21,000 compounds was conducted to identify potential RAD52 inhibitors. Molecular docking, molecular dynamics simulation (MD), density functional theory (DFT) analysis, and post-dynamics free energy calculations were performed. Five compounds with promising activities against RAD52 were identified. Compound 8758 showed the best inhibitory activity, followed by 10593, in terms of HOMO orbital energy and binding free energy calculations. Additionally, drug-like properties were observed for compounds 8758 and 10593. The results suggest that these small molecules could have therapeutic potential in managing breast cancer patients with BRCA mutations by targeting RAD52.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Shih-Chung Yen, Liang-Chieh Chen, Han-Li Huang, Wei-Chun HuangFu, Yi-Ying Chen, Ssu-Ting Lien, Hui-Ju Tseng, Tzu-Ying Sung, Jui-Hua Hsieh, Wei-Jan Huang, Shiow-Lin Pan, Kai-Cheng Hsu, Tony Eight Lin
Summary: A dual inhibitor, K783-0308, targeting FLT3 and MNK2, was identified in this study. It showed inhibitory effects on both FLT3 and MNK2, as well as promising results in suppressing AML cell growth and inducing cell cycle arrest.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Suyash Pant, Meenakshi Singh, V. Ravichandiran, U. S. N. Murty, Hemant Kumar Srivastava
Summary: The study identified potential protease inhibitors against SARS-CoV-2 using computational approaches, screening compounds from various databases and conducting docking and molecular dynamics simulations to find promising drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Physical
Kaushikkumar A. Bhakhar, Normi D. Gajjar, Kunjan B. Bodiwala, Dipen K. Sureja, Tejas M. Dhameliya
Summary: Tuberculosis is one of the top 10 causes of communicable disease deaths worldwide, and the mmpL3 target protein plays a crucial role in synthesizing essential components of the mycobacterial outer membrane. The search for new anti-tubercular agents through computational chemistry has provided a promising start in the field of molecular modeling for mmpL3 inhibitors.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Chemistry, Medicinal
Yuan-Rong Zheng, Chao-Jie Wang, Ling Yang, Yu-Jun Zhang, Mei-Juan Fang, He Chang, Kai-Qiang Guo, Song-Lin Shi
Summary: In this study, small molecule compounds that can interact with A2 protein were screened using computer virtual screening technology and BIAcore high-throughput screening system. The interactions between EpimedinA1, G38, hnRNPA2 proteins were confirmed using various experimental methods. Cell experiments showed that G38 inhibits the proliferation of breast cancer cells by targeting hnRNPA2 protein.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Article
Biochemical Research Methods
Tiantian Jian, Qing Su, Yan Liu, Hyuk-Kyu Seoh, John Edgar Houghton, Phang-Cheng Tai, Xinhe Huang
Summary: In this study, a structure-based virtual screening method was used to identify six novel anti-Helicobacter pylori compounds with new scaffolds against Helicobacter pylori SecA, an attractive antimicrobial target. The compounds showed stable behavior during molecular dynamics simulations and had favorable binding free energy values. ADME-T analysis indicated their druggability, further supporting their potential as lead compounds against Helicobacter pylori.
IEEE TRANSACTIONS ON NANOBIOSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Doretta Cuffaro, Aleix Gimeno, Bianca Laura Bernardoni, Riccardo Di Leo, Gerard Pujadas, Santiago Garcia-Vallve, Susanna Nencetti, Armando Rossello, Elisa Nuti
Summary: Scientists developed a virtual screening workflow to identify selective non-zinc-binding MMP-13 inhibitors by targeting its specific structural features. Three ligands that could inhibit MMP-13 in the micromolar range were discovered, and one of them showed selectivity over other MMPs. Structure-based analysis guided the chemical optimization, resulting in a new N-acyl hydrazone-based derivative with improved inhibitory activity and selectivity for the target enzyme.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Rong Xiang, Zhengsen Yu, Yang Wang, Lili Wang, Shanshan Huo, Yanbai Li, Ruiying Liang, Qinghong Hao, Tianlei Ying, Yaning Gao, Fei Yu, Shibo Jiang
Summary: The COVID-19 pandemic has caused chaos worldwide, with vaccines in distribution but treatment methods lagging behind. Researchers are working hard to understand the virus and develop effective treatments.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biochemistry & Molecular Biology
Andres Felipe Vasquez, Luis Alberto Gomez, Andres Gonzalez Barrios, Diego M. Riano-Pachon
Summary: Antifolates like methotrexate block nucleic acid synthesis and cell proliferation, but their classical structure is ineffective against melanoma. A study combining virtual screening and cell-based assays identified promising non-classical hDHFR inhibitors, with compounds C1 and C2 exhibiting activity against melanoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nicolas Rosa, Hristina Ivanova, Larry E. Wagner, Justin Kale, Rita La Rovere, Kirsten Welkenhuyzen, Nikolaos Louros, Spyridoula Karamanou, Victoria Shabardina, Irma Lemmens, Elien Vandermarliere, Kozo Hamada, Hideaki Ando, Frederic Rousseau, Joost Schymkowitz, Jan Tavernier, Katsuhiko Mikoshiba, Anastassios Economou, David W. Andrews, Jan B. Parys, David Yule, Geert Bultynck
Summary: The study shows that Bcl-xL and Bcl-2 have similar anti-apoptotic effects in controlling endoplasmic reticulum Ca2+ release, challenging the current understanding of their divergent functions in Ca2+ signaling modulation.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Johana Hrdinova, Delia I. Fernandez, Bogac Ercig, Bibian M. E. Tullemans, Dennis P. L. Suylen, Stijn M. Agten, Kerstin Jurk, Tilman M. Hackeng, Karen Vanhoorelbeke, Jan Voorberg, Chris P. M. Reutelingsperger, Kanin Wichapong, Johan W. M. Heemskerk, Gerry A. F. Nicolaes
Summary: This study designed and synthesized stable cyclic peptides to interfere with the interaction between VWF A1 domain and GPIb alpha. The selected peptides showed low binding free energy and retained their interference in the binding of VWF to GPIb-V-IX, as confirmed by flow cytometry. These peptides phenotypically mimicked the changes seen with the anti-VWF A1 domain antibody CLB-RAg35, although they were less potent. The improved peptide opt-mono-ORbIT demonstrated increased inhibitory activity under flow.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Biao Yuan, Athina G. Portaliou, Rinky Parakra, Jochem H. Smit, Jiri Wald, Yichen Li, Bindu Srinivasu, Maria S. Loos, Harveer Singh Dhupar, Dirk Fahrenkamp, Charalampos G. Kalodimos, Franck Duong van Hoa, Thorben Cordes, Spyridoula Karamanou, Thomas C. Marlovits, Anastassios Economou
Summary: Type III protein secretion is common in Gram-negative pathogens, with SctV forming peripheral oligomeric clusters in EPEC and serving as a key receptor for different chaperone/exported protein pairs. The dynamic motions of SctV protomers, modulated by chaperones and ATPase, may allosterically affect the secretion process.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Srinath Krishnamurthy, Marios-Frantzeskos Sardis, Nikolaos Eleftheriadis, Katerina E. Chatzi, Jochem H. Smit, Konstantina Karathanou, Giorgos Gouridis, Athina G. Portaliou, Ana-Nicoleta Bondar, Spyridoula Karamanou, Anastassios Economou
Summary: Protein machines undergo conformational motions to interact with and manipulate polymeric substrates. The intrinsic dynamics of Sec translocase ATPase, SecA, and the binding of preproteins combine to achieve translocation. This universal mechanism allows any preprotein to undergo translocation and be secreted.
Article
Biochemical Research Methods
Hessel Poelman, Hans Ippel, Berke Gurkan, Rolf Boelens, Gert Vriend, Cornelis van 't Veer, Esther Lutgens, Gerry A. F. Nicolaes
Summary: Researchers elucidated the structure of IRAK-M death domain using NMR and performed docking studies to reveal its position in the Myddosome and the molecular basis for its selectivity towards IRAK1 over IRAK2 binding. They identified structural issues in the original model and built a more accurate homology model based on high-resolution crystal structures, which better matched known information about the death domain structure.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Review
Biochemistry & Molecular Biology
Angelina Pavlic, Nasim Bahram Sangani, Johanna Kerins, Gerry Nicolaes, Leon Schurgers, Chris Reutelingsperger
Summary: Vascular calcification is the pathological deposition of calcium salts in blood vessel walls and is a risk factor for cardiovascular events and mortality. Vascular smooth muscle cells (VSMCs) play a crucial role in this process by releasing extracellular vesicles (EVs), but the underlying mechanisms are not fully understood. Understanding the molecular factors and mechanisms of EV release is essential for developing targeted pharmacological treatments for vascular calcification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Dries Smets, Jochem Smit, Ying Xu, Spyridoula Karamanou, Anastassios Economou
Summary: Signal peptides delay folding by crosstalking with mature domains, altering the folding landscape of proteins.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Medicine, General & Internal
Rickard Lagedal, Oskar Eriksson, Anna Sorman, Joram B. Huckriede, Bjarne Kristensen, Stephanie Franzen, Anders Larsson, Anders Bergqvist, Kjell Alving, Anders Forslund, Barbro Persson, Kristina N. Ekdahl, Pablo Garcia de Frutos, Bo Nilsson, Gerry A. F. Nicolaes, Miklos Lipcsey, Michael Hultstrom, Robert Frithiof
Summary: The antibody response in critically ill patients with COVID-19 is associated with organ failure, systemic histone release, and increased 30-day mortality.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Dries Smets, Alexandra Tsirigotaki, Jochem H. Smit, Srinath Krishnamurthy, Athina G. Portaliou, Anastassia Vorobieva, Wim Vranken, Spyridoula Karamanou, Anastassios Economou
Summary: This study investigates the delayed folding mechanism and the regulatory role of signal peptides in the Sec pathway. By comparing two homologous proteins, PpiA and PpiB, it is found that PpiA folds slower and the folding process involves hierarchical foldons. The folding of PpiA is delayed by less hydrophobic native contacts, frustrated residues, and a beta-turn in the earliest foldon, as well as by signal peptide-mediated disruption of foldon hierarchy. Additionally, grafting selected residues or the signal peptide of PpiA onto PpiB converts it into a slow folder with enhanced in vivo secretion. These structural adaptations facilitate protein trafficking.
Article
Biochemistry & Molecular Biology
Angelina Pavlic, Hessel Poelman, Grzegorz Wasilewski, Kanin Wichapong, Petra Lux, Cecile Maassen, Esther Lutgens, Leon J. Schurgers, Chris P. Reutelingsperger, Gerry A. F. Nicolaes
Summary: Vascular calcification (VC) is an important factor in cardiovascular diseases, mediated by the release of extracellular vesicles by vascular smooth muscle cells (VSMCs) and the enzyme nSMase2. Inhibitors of nSMase2 have been identified through virtual ligand screening, and two compounds (ID 5728450 and ID 4011505) were found to inhibit EV release and calcification in vitro, potentially serving as therapeutic drugs for VC treatment or prevention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Femke de Vries, Joram Huckriede, Kanin Wichapong, Chris Reutelingsperger, Gerry A. F. Nicolaes
Summary: This article reviews the cytotoxic mechanisms of extracellular histones in COVID-19 and discusses their role as potential drug targets and biomarkers. It provides important insights for the clinical treatment of COVID-19 patients.
JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Tim C. van Smaalen, Danielle M. H. Beurskens, Jasper J. H. F. M. Kox, Rasheendra Polonia, Rein Vos, Hans Duimel, Willine J. van de Wetering, Carmen Lopez-Iglesias, Chris P. Reutelingsperger, L. W. Ernest van Heurn, Carine J. Peutz-Kootstra, Gerry A. F. Nicolaes
Summary: Extracellular histones are released in warm ischemia and the resulting damage can be prevented by blocking histone release. The release of extracellular histones in patients receiving a renal transplant is associated with worse graft outcome. The findings suggest that targeting histones may be beneficial in preventing renal injury during transplantation.
Article
Medicine, General & Internal
Martine E. Bol, J. B. Huckriede, K. G. H. van de Pas, T. Delhaas, R. Lorusso, G. A. F. Nicolaes, J. E. M. Sels, M. C. G. van de Poll
Summary: This study aimed to compare different indices of glycocalyx shedding and dysfunction in patients undergoing coronary artery bypass grafting (CABG) surgery. The results showed that glycocalyx thinning was accompanied by impaired glycocalyx function and increased endothelial activation during CABG surgery with cardiopulmonary bypass (CPB).
FRONTIERS IN MEDICINE
(2022)
Article
Hematology
Joram B. Huckriede, Danielle M. H. Beurskens, Karin C. C. A. Wildhagen, Chris P. M. Reutelingsperger, Kanin Wichapong, Gerry A. F. Nicolaes
Summary: This study investigated the interaction between human APC and human histone H3 and designed optimized APC variants through molecular docking and molecular dynamics simulation methods. The results showed that the designed APC variants had reduced anticoagulant activity, increased binding to histone H3, and similar ability to proteolyze histone H3 compared to the wild type-APC.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)