A5001392142- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- Protein Structure and Dynamics
- Chemical Synthesis and Analysis
- SARS-CoV-2 and COVID-19 Research
- Catalytic C–H Functionalization Methods
- Epigenetics and DNA Methylation
- Biochemical and Molecular Research
- Synthesis and biological activity
- Protein Degradation and Inhibitors
- Cholinesterase and Neurodegenerative Diseases
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Catalytic Alkyne Reactions
- Asymmetric Synthesis and Catalysis
- Signaling Pathways in Disease
- Click Chemistry and Applications
- Cancer-related gene regulation
- Catalytic Cross-Coupling Reactions
- Enzyme Structure and Function
- Ion channel regulation and function
- Quinazolinone synthesis and applications
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Amino Acid Enzymes and Metabolism
Shanghai Institute of Materia Medica
2016-2025
Chinese Academy of Sciences
2016-2025
ShanghaiTech University
2016-2025
Nanjing University of Chinese Medicine
2020-2025
University of Chinese Academy of Sciences
2005-2024
East China University of Science and Technology
2012-2023
China Pharmaceutical University
2002-2023
Institute for Advanced Study
2023
University of Minnesota
2023
National Center for Drug Screening
2021-2023
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, Mpro, a key enzyme that plays pivotal role in mediating viral replication and transcription. We designed synthesized two lead compounds (11a 11b) targeting Mpro Both exhibited excellent inhibitory activity potent anti-SARS-CoV-2 infection activity. x-ray crystal structures complex with 11a or 11b, both...
The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS-CoV-2), has become a global crisis. Replication SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp) enzyme, target antiviral drug remdesivir. Here we report cryo-electron microscopy structure RdRp, both in apo form at 2.8-angstrom resolution and complex with 50-base template-primer remdesivir 2.5-angstrom resolution. reveals that partial double-stranded template is inserted...
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...
In silico drug target identification, which includes many distinct algorithms for finding disease genes and proteins, is the first step in discovery pipeline. When 3D structures of targets are available, problem identification usually converted to best interaction mode between potential candidates small molecule probes. Pharmacophore, spatial arrangement features essential a interact with specific receptor, an alternative method achieving this goal apart from molecular docking method....
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...
CCR5-Maraviroc Structure The chemokine receptor CCR5, a G protein–coupled best known as co-receptor during HIV-1 infection, is important in variety of physiological processes. Tan et al. (p. 1387 , published online 12 September; see the Perspective by Klasse ) now report high-resolution crystal structure CCR5 bound to entry inhibitor, Maraviroc. suggests that Maraviroc acts noncompetitive inhibitor binding region distinct from site and chemokines. Comparison with other co-receptor, CXCR4,...
Two human demethylases, the fat mass and obesity-associated (FTO) enzyme ALKBH5, oxidatively demethylate abundant N6-methyladenosine (m6A) residues in mRNA. Achieving a method for selective inhibition of FTO over ALKBH5 remains challenge, however. Here, we have identified meclofenamic acid (MA) as highly inhibitor FTO. MA is non-steroidal, anti-inflammatory drug that mechanistic studies indicate competes with binding m6A-containing nucleic acid. The structure FTO/MA has revealed much about...
Although recognized in small molecules for quite some time, the implications of halogen bonding biomolecular systems are only now coming to light. In this study, several proteins complex with halogenated ligands have been investigated by using a two-layer QM/MM ONIOM methodology. all cases, halogen−oxygen distances shown be much less than van der Waals radius sums. Single-point energy calculations unveil that interaction becomes comparable magnitude classical hydrogen bonding. Furthermore,...
Musical Chairs The plant hormone abscisic acid (ABA) helps plants to respond changes in the environment, such as drought. Physiological responses are initiated when ABA binds its receptor. In absence of ABA, downstream kinases held inactive by phosphatases. Soon et al. (p. 85 , published online 24 November; see Perspective Leung ) now show that both hormone-receptor complex and kinase bind same site on phosphatase. Thus, presence hormone, phosphatase is occupied unable interfere with activity.
Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report crystal structures 5-HT1B G protein-coupled bound to agonist antimigraine medications ergotamine and dihydroergotamine. The reveal similar binding modes for these ligands, which occupy orthosteric pocket an extended close extracellular loops. is formed by residues conserved in family, clarifying family-wide activity 5-HT. Compared with structure 5-HT2B receptor,...
TarFisDock is a web-based tool for automating the procedure of searching small molecule–protein interactions over large repertoire protein structures. It offers PDTD (potential drug target database), database containing 698 structures covering 15 therapeutic areas and reverse ligand–protein docking program. In contrast to conventional docking, aims seek potential targets by screening an appropriate database. The input file this web server molecule be tested, in standard mol2 format; then...
The direct nucleic acid repair dioxygenase FTO is an enzyme that demethylates N6-methyladenosine (m6A) residues in mRNA vitro and inside cells. the first RNA demethylase discovered also serves a major regulatory function mammals. Together with structure-based virtual screening biochemical analyses, we report identification of several small-molecule inhibitors human demethylase. most potent compound, natural product rhein, which neither structural mimic 2-oxoglutarate nor chelator metal ion,...
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...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report structures of spike trimer on its own and in complex with angiotensin-converting enzyme (ACE2) or an anti-Omicron antibody. Most mutations are located surface protein change binding epitopes to many current antibodies. In ACE2-binding site, compensating strengthen receptor domain (RBD) ACE2. Both RBD apo form thermodynamically unstable. An unusual RBD-RBD...