Publications by authors named "Leyun Wu"
Article Synopsis
- ATPases Associated with Diverse Cellular Activity (AAAATPases) are crucial proteins in human cells, with TRIP13 being a significant member that helps regulate DNA repair and mitosis.
- TRIP13 is linked to various cancers, serving as an oncogene involved in multiple malignancy pathways, and its structure aids in understanding its interactions with other proteins, particularly in cell division.
- This review consolidates information on TRIP13's biological roles in eighteen cancers, highlights four small-molecule inhibitors that target TRIP13, and discusses its potential as an effective anticancer drug target.
Article Synopsis
- Halogen bonds (XBs) are important for molecular recognition and drug design, but research has primarily focused on halogenated ligands rather than naturally occurring or specially prepared halogenated residues (hr_XBs).
- This study utilized computational methods like database searches and molecular dynamics simulations to investigate hr_XBs in proteins and peptides, revealing that XBs at protein-peptide interfaces can enhance binding affinities.
- It also found that intramolecular XBs (intra_XBs) contribute to structural stability in flexible proteins, while their absence can reduce stability in proteins that are already rigid.
Article Synopsis
- - Halogenation is a key technique used to modify lead compounds, enhancing their lipophilicity for better membrane permeability and bioavailability.
- - In this study, 19.9% of organohalogen compounds showed increased water solubility compared to their non-halogenated versions, with iodination being the most effective.
- - The presence of groups like amino, hydroxyl, and carboxyl in organohalogens boosts their solubility, while a trifluoromethyl group decreases it; increased polarity and polarizability from halogenation contribute to these changes.
Article Synopsis
- Continuous exploration of chemical space is vital in drug discovery, focusing on cyclic compounds, especially natural ones with varied structures, which offer unique insights for new drug designs.
- A novel method called D3Rings was developed to systematically identify different types of ring compounds, and extensive data analysis was conducted using three major chemical databases, highlighting the diversity of cyclic structures in natural products.
- The creation of larger datasets and subsequent docking experiments revealed that cyclic structures showed the best results for potential drug candidates against SARS-CoV-2, emphasizing the need for expanding the library of cyclic compounds in drug research.
Discovery of zolinium TSG1180 as a novel agonist of transgelin-2 for treating asthma.
Biomed Pharmacother
November 2023
Article Synopsis
- Asthma is a complicated respiratory disease that significantly impacts individuals and society, often not fully controllable with existing medications like β-agonists.
- Researchers identified a zolinium compound, TSG1180, which strongly interacts with Transgelin-2, a potential target for alleviating asthma symptoms, demonstrating effective results in various assays.
- TSG1180 not only relaxed airway smooth muscle cells in vitro but also significantly reduced pulmonary resistance in a mouse model, indicating its potential as a new treatment option for asthma that works specifically through Transgelin-2.
Article Synopsis
- Traditional drug discovery is resource-heavy, necessitating advanced computational tools for drug-target interaction (DTI) prediction due to inefficiencies in existing methods.
- The study introduces D3CARP, a comprehensive webserver that uses multiple methods including docking, ligand similarity searches, and deep learning to enhance target prediction and virtual screening.
- With high accuracies (0.89 for deep learning and 0.94 for ligand similarity), D3CARP provides a robust platform for drug discovery, complete with disease annotations and positive controls, available for free online.
Article Synopsis
- Hydrogen bonds (HBs) and halogen bonds (XBs) are key interactions in molecular recognition and drug design, influenced by the diverse structures of proteins and their surrounding environments.
- This study introduced local hydrophobicities (LHs) and local dielectric constants (LDCs) to examine the microenvironments of 22,011 ligand-protein structures, finding that XBs favor hydrophobic conditions more than HBs.
- Results indicate that polar residues like ASP are more likely to form HBs, whereas nonpolar residues such as PHE and MET lean towards XBs, with quantum mechanics calculations showing that HBs are generally weaker than XBs in varied environments.
Global dynamics and pattern formation for predator-prey system with density-dependent motion.
Math Biosci Eng
January 2023
Article Synopsis
- - The paper examines a predator-prey model with a generalist predator and prey that show density-dependent movements in a two-dimensional space.
- - It establishes the existence of classical solutions and proves global stability of steady states using Lyapunov functionals, ensuring consistent behavior over time.
- - The study finds that if the prey's movement increases with its density, it can lead to the emergence of periodic patterns, confirmed through linear analyses and numerical simulations.
Article Synopsis
- Transgelin-2 (TG2) is identified as a promising target for asthma treatment due to its role in relaxing airway muscles and lowering pulmonary resistance.
- The study utilized 12.6 μs molecular dynamics simulations to analyze both the unbound form of TG2 and its complex with the agonist TSG12, revealing four main conformations of TG2 and three binding sites for TSG12.
- Key residues E27, R49, and F52 were highlighted as crucial for TSG12 binding, offering insights into TG2’s dynamic behavior and aiding in future anti-asthma drug development.
Article Synopsis
- * Results from molecular dynamics simulations and ELISA tests indicate that both Delta and Omicron spike proteins have enhanced binding capacities to ACE2, suggesting a higher potential for cell infection.
- * Analysis of protein interactions reveals that both mutated and conserved sites contribute to stronger binding, which raises concerns about immune evasion and has implications for developing effective antibodies and treatments.
Article Synopsis
- * The D3AI-CoV platform utilizes three innovative deep learning models to enhance target prediction and virtual screening, demonstrating superior performance compared to existing methods.
- * D3AI-CoV is accessible as a free web application, allowing users to quickly identify potential drug targets and active compounds for COVID-19 treatment.
Article Synopsis
- There are 7 known human pathogenic coronaviruses, and due to the current epidemic caused by SARS-CoV-2, experts anticipate new coronaviruses may arise in the future.
- The study analyzed the virus-encoded proteins from these coronaviruses to find highly conserved proteins and binding sites, crucial for creating broad-spectrum anti-coronavirus drugs.
- Researchers identified six conserved proteins (nsp5, nsp10, nsp12, nsp13, nsp14, and nsp16) with low similarity to human proteins, suggesting they are promising targets for developing effective pan-coronavirus medications.
Article Synopsis
- - The COVID-19 pandemic was caused by the SARS-CoV-2 virus, and its spike protein, particularly the N-terminal domain (NTD), is crucial for understanding immune response, but less researched than the receptor-binding domain (RBD).
- - This study used molecular dynamics simulations to identify 36 critical residues on the NTD that interact with neutralizing antibodies, highlighting potential risks for immune evasion from mutations.
- - Notably, the R246I mutation found in the Beta variant (B.1.351/501Y.V2) can weaken antibody binding by disrupting essential interactions, signalling the need for careful monitoring of NTD mutations in future vaccine and antibody development.
Article Synopsis
- Current COVID-19 vaccines are struggling against new SARS-CoV-2 variants, particularly those with the E484K mutation, which show significant resistance to neutralization by vaccine-induced antibodies.* -
- A study analyzed the binding affinities of 26 antibodies to both the wild-type spike protein and the E484K variant, revealing that approximately 85% of antibodies bind less effectively to the mutated version, mainly due to the differences in amino acid interactions.* -
- Notably, a monoclonal antibody combination demonstrated stronger binding to the E484K variant than to the wild type, suggesting potential for effective treatment, while also predicting that mutations in four additional residues could pose further risks of immune evasion.*