A5105978526- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Chemical Synthesis and Analysis
- Crystallization and Solubility Studies
- Protein Degradation and Inhibitors
- X-ray Diffraction in Crystallography
- Natural product bioactivities and synthesis
- Phytochemistry and Biological Activities
- Crystallography and molecular interactions
- Bioactive Compounds and Antitumor Agents
- Cholinesterase and Neurodegenerative Diseases
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- Catalytic C–H Functionalization Methods
- Enzyme Structure and Function
- Analytical Chemistry and Chromatography
- DNA and Nucleic Acid Chemistry
- Click Chemistry and Applications
- Synthesis and biological activity
- Neuropeptides and Animal Physiology
- Catalytic Cross-Coupling Reactions
- Iron Metabolism and Disorders
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Multiple Myeloma Research and Treatments
Shanghai Institute of Materia Medica
2016-2025
Chinese Academy of Sciences
2016-2025
Shanghai University of Traditional Chinese Medicine
2016-2025
University of Chinese Academy of Sciences
2018-2025
State Administration of Traditional Chinese Medicine of the People's Republic of China
2024-2025
Nanjing University of Chinese Medicine
2019-2025
China Pharmaceutical University
2002-2024
Fudan University
2001-2024
ShanghaiTech University
2014-2023
State Key Laboratory of Drug Research
2013-2023
Protein-protein interactions (PPIs) are central to most biological processes. Although efforts have been devoted the development of methodology for predicting PPIs and protein interaction networks, application existing methods is limited because they need information about homology or marks partners. In present work, we propose a method PPI prediction using only sequences. This was developed based on learning algorithm-support vector machine combined with kernel function conjoint triad...
Hunting for chemicals with favorable pharmacological, toxicological, and pharmacokinetic properties remains a formidable challenge drug discovery. Deep learning provides us powerful tools to build predictive models that are appropriate the rising amounts of data, but gap between what these neural networks learn human beings can comprehend is growing. Moreover, this may induce distrust restrict deep applications in practice. Here, we introduce new graph network architecture called Attentive...
Halogen bond has attracted a great deal of attention in the past years for hit-to-lead-to-candidate optimization aiming at improving drug-target binding affinity. In general, heavy organohalogens (i.e., organochlorines, organobromines, and organoiodines) are capable forming halogen bonds while organofluorines not. order to explore possible roles that could play beyond affinity, we performed detailed database survey quantum chemistry calculation with close paid (1) change ratio along drug...
Abstract Motivation Identifying compound–protein interaction (CPI) is a crucial task in drug discovery and chemogenomics studies, proteins without three-dimensional structure account for large part of potential biological targets, which requires developing methods using only protein sequence information to predict CPI. However, sequence-based CPI models may face some specific pitfalls, including inappropriate datasets, hidden ligand bias splitting datasets inappropriately, resulting...
Long Stokes shift dyes that minimize cross-talk between the excitation source and fluorescent emission to improve signal-to-background ratio are highly desired for fluorescence imaging. However, simple small molecular with large (more than 120 nanometers) near-infrared (NIR) emissions have been rarely reported so far. Here, inspired by chromophore chemical structure of proteins, we designed synthesized a series styrene oxazolone (SODs) synthetic methods, which show NIR (>650 long (ranged...
Abstract Background Target identification is important for modern drug discovery. With the advances in development of molecular docking, potential binding proteins may be discovered by docking a small molecule to repository with three-dimensional (3D) structures. To complete this task, reverse program and target database 3D structures are necessary. end, we have developed web server tool, TarFisDock ( Tar get Fis hing Dock ing) http://www.dddc.ac.cn/tarfisdock , which has been used widely...
The amyloid β-peptides (Aβs), containing 39–43 residues, are the key protein components of deposits in Alzheimer's disease. To structurally characterize dynamic behavior Aβ 40 , 12 independent long-time molecular dynamics (MD) simulations for a total 850 ns were performed on both wide-type peptide and its mutant aqueous solution biomembrane environment. In solution, an α-helix to β-sheet conformational transition was observed, entire unfolding process from helix coil traced by MD simulation....
ABSTRACT The 3C-like proteinase (3CL pro ) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one the most promising targets for anti-SARS-CoV drugs due to its crucial role in viral life cycle. In this study, a database containing structural information more than 8,000 existing was virtually screened by docking approach identify potential binding molecules SARS-CoV 3CL . As target screening, both homology model and crystallographic structure pocket enzyme were used....
A series of novel thiosemicarbazone derivatives bearing condensed heterocyclic carboxaldehyde moieties were designed and synthesized. Among them, TSC24 exhibited broad antiproliferative activity in a panel human tumor cells suppressed growth mice. The mechanism research revealed that was not only an iron chelator but also topoisomerase IIα catalytic inhibitor. Its inhibition on due to direct interaction with the ATPase domain which led block ATP hydrolysis. Molecular docking predicted might...
Peptidic mimics of the gut hormone glucagon-like peptide (GLP) 1, exemplified by recently approved drug exenatide, show promise as therapies for type 2 diabetes. Such "incretin mimetics" regulate glucose appearance in plasma and can restore glucose-stimulated insulin secretion without excess risk hypoglycemia. The need injection, which may limit use peptidic GLP-1 receptor (GLP-1R) agonists, has driven largely unsuccessful efforts to find smaller molecules. failure identify orally effective...
Economical nanocomposites based on π-stacking of N-acetyl glycosyl rhodamine B to graphene oxide (GO) are simply prepared. These "sweet" GO-materials proven be admirable for the fluorogenic recognition specific intercellular sugar-based ligand-glycoprotein receptor interactions interest.
For proof-of-concept of halogen bonding in drug design, a series halogenated compounds were designed based on lead structure as new inhibitors phosphodiesterase type 5. Bioassay results revealed good correlation between the measured bioactivity and calculated bond energy. Our X-ray crystal structures verified existence predicted bonds, demonstrating that is an applicable tool design should be routinely considered optimization.
Polycomb Repressive Complex 2 (PRC2) modulates the chromatin structure and transcriptional repression by trimethylation lysine 27 of histone H3 (H3K27me3), a process that necessitates protein–protein interaction (PPI) between catalytic subunit EZH2 EED. Deregulated PRC2 is intimately involved in tumorigenesis progression, making it an invaluable target for epigenetic cancer therapy. However, until now, there have been no reported small molecule compounds targeting EZH2-EED interactions. In...
Abstract Benzoxepane derivatives were designed and synthesized, one hit compound emerged as being effective in vitro with low toxicity. In vivo, this ameliorated both sickness behavior through anti‐inflammation LPS‐induced neuroinflammatory mice model cerebral ischemic injury anti‐neuroinflammation rats subjected to transient middle artery occlusion. Target fishing for the using photoaffinity probes led identification of PKM2 target protein responsible anti‐inflammatory effect compound....
The kinome-wide virtual profiling of small molecules with high-dimensional structure–activity data is a challenging task in drug discovery. Here, we present model against panel 391 kinases based on large-scale bioactivity and the multitask deep neural network algorithm. obtained yields excellent internal prediction capability an auROC 0.90 consistently outperforms conventional single-task models external tests, especially for insufficient activity data. Moreover, more rigorous experimental...
A novel series of peptidomimetic aldehydes was designed and synthesized to target 3C protease (3Cpro) enterovirus 71 (EV71). Most the compounds exhibited high antiviral activity, among them, compound 18p demonstrated potent enzyme inhibitory activity broad-spectrum on a panel enteroviruses rhinoviruses. The crystal structure EV71 3Cpro in complex with determined at resolution 1.2 Å revealed that covalently linked catalytic Cys147 an aldehyde group. In addition, these also good against 3CLpro...
Abstract The autophagic ubiquitin‐like protein LC3 functions through interactions with LC3‐interaction regions (LIRs) of other autophagy proteins, including receptors, which stands out as a promising protein–protein interaction (PPI) target for the intervention autophagy. Post‐translational modifications like acetylation Lys49 on LIR‐interacting surface could disrupt interaction, offering an opportunity to design covalent small molecules interfering interface. Through screening compounds, we...
This study describes a novel aqueous reaction for the synthesis of (<italic>Z</italic>)-enaminones through combination heterogeneous catalysis and photocatalysis.
The nucleocapsid (N) protein of SARS coronavirus (SARS_CoV) is a major structural component virions, which appears to be multifunctional involved in viral RNA replication and translation. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) related the pre‐mRNA splicing nucleus translation regulation cytoplasm. In this report, based on relevant biophysical biochemical assays, SARS_CoV (SARS_N) was discovered exhibit high binding affinity human hnRNP A1. GST pull‐down results clearly...
We developed a simple and convenient copper-catalyzed method for the synthesis of quinoline-2-carboxylate derivatives through sequential intermolecular addition alkynes onto imines subsequent intramolecular ring closure by arylation. The efficiency this system allowed reactions to be carried out at room temperature.