A5009654446- Protein Structure and Dynamics
- Pharmacogenetics and Drug Metabolism
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- Drug Transport and Resistance Mechanisms
- Analytical Chemistry and Chromatography
- Crystallization and Solubility Studies
- DNA and Nucleic Acid Chemistry
- X-ray Diffraction in Crystallography
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Cancer therapeutics and mechanisms
- Glycosylation and Glycoproteins Research
- Influenza Virus Research Studies
- HIV/AIDS drug development and treatment
- Organic Light-Emitting Diodes Research
- Biochemical and Molecular Research
- Enzyme function and inhibition
- Protein Kinase Regulation and GTPase Signaling
- Redox biology and oxidative stress
- Lung Cancer Treatments and Mutations
- Protein Tyrosine Phosphatases
- Peptidase Inhibition and Analysis
Jilin University
2016-2025
Jilin Medical University
2009-2024
Jiangnan University
2024
Taiyuan Heavy Industry (China)
2024
Institute of Theoretical Physics
2011-2021
State Council of the People's Republic of China
2015-2020
Joint Research Center
2020
First Hospital of Jilin University
2019
Yantai University
2009
Heilongjiang University
2008
It is commonly observed that hydrophobic molecules alone cannot self-assemble into stable nanoparticles, requiring amphiphilic or ionic materials to support nanoparticle stability and function in vivo. We report herein newly self-assembled nanomedicines through entirely different mechanisms. present proof-of-concept methodology results of our hypothesis disulfide-induced (DSINMs) are promoted stabilized by the insertion a single disulfide bond molecules, order balance competition between...
The polarization of tumor-associated macrophages (TAMs) from M2 to M1 phenotype demonstrates great potential for remodeling the immunosuppressive tumor microenvironment (TME) hepatocellular carcinoma (HCC). d-lactate (DL; a gut microbiome metabolite) acts as an endogenous immunomodulatory agent that enhances Kupffer cells clearance pathogens. In this study, DL transformation TAMs was confirmed, and mechanisms underlying such were mainly due modulation phosphatidylinositol 3-kinase/protein...
Abstract The structural variability data of drug transporter (DT) are key for research on precision medicine and rational use. However, these valuable not sufficiently covered by the available databases. In this study, a major update VARIDT (a database previously constructed to provide DTs’ data) was thus described. First, experimentally resolved structures all DTs reported in original were discovered from PubMed Protein Data Bank. Second, each DT collected literature review, which included:...
Abstract Alectinib, a highly selective next‐genetation anaplastic lymphoma kinase (ALK) inhibitor, has demonstrated promising antitumor activity in patients with ALK‐positive non‐small cell lung carcinomas (NSCLC). However, the therapeutic benefits of alectinib is inescapably hampered by development acquired resistant mutations ALK. Despite availability ample experimental mutagenesis data, molecular origin and structural motifs under binding affinity deficiencies are still ambiguous. Here,...
The EDG/EWG modified NATs were successfully developed as a new class of organic solid fluorophores with tunable emission from the blue to yellow light region.
Unregulated livestock breeding and grazing can degrade grasslands damage the ecological environment. The combination of remote sensing artificial intelligence techniques is a more convenient powerful means to acquire information in large area than traditional manual ground investigation. As mainstream platform, unmanned aerial vehicles (UAVs) obtain high-resolution optical images detect grassland. However, objects UAV usually occupy very few pixels tend gather together, which makes them...
The parathyroid hormone type 1 receptor (PTH1R) plays a crucial role in modulating various physiological functions and is considered an effective therapeutic target for osteoporosis. However, lack of detailed molecular energetic information about PTH1R limits our comprehensive understanding its activation process. In this study, we performed computational simulations to explore key events the process, such as conformational changes PTH1R, Gs protein coupling, release guanosine diphosphate...
Heptachlor (HEP) is an insecticide metabolized by cytochrome P450 (CYP) enzymes in the human liver, resulting formation of heptachlor epoxide (HEPX). HEPX can persist body for a long duration. Therefore, it be extremely harmful. A comprehensive understanding HEP's metabolic fate may provide theoretical basis mitigating associated hazards. However, specific CYP isoforms that metabolize HEP, and their mechanisms, remain unclear. In this study, eight were used as catalytic to investigate...
Abstract Cytochrome P450 (CYP) 7B1 is a steroid cytochrome 7α‐hydroxylase that has been linked directly with bile salt synthesis and hereditary spastic paraplegia type 5 (SPG5). The enzyme provides the primary metabolic route for neurosteroids dehydroepiandrosterone (DHEA), cholesterol derivatives 25‐hydroxycholesterol (25‐HOChol), other steroids such as 5α‐androstane‐3β,17β‐diol (anediol), 5α‐androstene‐3β,17β‐diol (enediol). A series of investigations including homology modeling, molecular...
Cytochrome P450 (CYP) 17A1 is a dual-function monooxygenase with critical role in the synthesis of many human steroid hormones. The enzyme an important target for treatment breast and prostate cancers that proliferate response to estrogens androgens. Despite ample experimental mutagenesis data, molecular origin structural motifs enzymatic activities deficiencies have not been rationalized at atomic resolution. To this end, we investigated effects on characteristics tunnel geometry upon...
In this study, we designed two series of novel anthraquinone-based benzenesulfonamide derivatives and their analogues as potential carbonic anhydrase inhibitors (CAIs) evaluated inhibitory activities against off-target human II (hCA II) isoform tumor-associated IX IX) isoform. Most these compounds exhibited good hCA IX. The that the best inhibition were further studied MDA-MB-231, MCF-7, HepG2 cell lines under hypoxic normoxic conditions. Additionally, exhibiting antitumor activity subjected...
Abstract Iridium(III) complexes with N ‐heterocyclic (NHC) ligands including fac ‐Ir(pmb) 3 (1), mer (2), (pmb) 2 Ir(acac) (3), ‐Ir(pypi) (4), and (5) [pmb = 1‐phenyl‐3 H ‐benzimidazolin‐2‐ylidene, acac acetoylacetonate, pypi 1‐phenyl‐5 ‐benzimidazolin‐2‐ylidene; facial, meridional ] were investigated theoretically. The geometry structures of 1–5 in the ground excited state optimized restricted unrestricted DFT (density functional theory) methods, respectively (LANL2DZ for Ir atom 6‐31G...
The research on the binding process of ligand to pyrazinamidase (PncA) is crucial for elucidating inherent relationship between resistance Mycobacterium tuberculosis and PncA's activity. In present study, molecular dynamics (MD) simulation methods were performed investigate unbinding nicotinamide (NAM) from two PncA enzymes, which reverse corresponding process. calculated potential mean force (PMF) based steered (SMD) simulations sheds light an optimal binding/unbinding pathway ligand....
α-Hemolysin (Hla) is a significant virulence factor in Staphylococcus aureus (S. aureus)-infected disease such as pneumonia. So, it necessary to choose an antibiotic that having good antibacterial activity and effect on preventing the production of Hla so treat S. infection. In our study, we observed Fosfomycin (FOM) inhibited expression at sub-inhibitory concentration. Molecular dynamics demonstrated FOM bound binding sites LYS 154 ASP 108 Hla, which may cause inhibition Hla. Furthermore,...
MD simulations, MM-PBSA, and SIE analyses were used to investigate the drug resistance mechanisms of two mutations G48T L89M in HIV-1 protease toward four inhibitors.
The sterol 14α demethylase enzyme (CYP51) is an important target of fungal infections. However, the molecular mechanism between triazoles inhibitors and CYP51 remains obscure. In this study, we have investigated binding tunnel characteristic upon four with based on docking dynamics simulations. results indicate stabilize in cavity a similar mode. We discover hydrophobic (F58, Y64, Y118, L121, Y132, L376, S378, S506, S507, M508) interaction main driving force for to CYP51. long-tailed...
The one-electron reduction product, ˙CCl<sub>3</sub>, irreversibly inactivates P450 <italic>via</italic> covalently binding to the <italic>meso</italic>-carbon, whereas two successive reductions :CCl<sub>2</sub>, reversibly inhibits by coordinating iron.
Karrikins (KARs) are a class of smoke-derived seed germination stimulants with great significance in both agriculture and plant biology. By means direct binding to the receptor protein KAI2, compounds can initiate KAR signal transduction pathway, hence triggering dormant seeds soil. In research, several molecular dynamics (MD) simulation techniques were properly integrated investigate process KAR1 KAI2 reveal details whole event. The calculated free energy, −7.00 kcal/mol, is good agreement...
Human immunodeficiency virus type 1 (HIV-1) protease is regarded as a fascinating target for drug development against HIV infection. However, mutations causing resistance severely limit the efficiency of recently marketed drugs in treatment replication. To elucidate binding mechanism HIV-1 with promising inhibitor GRL-02031 and further to probe associated (I47V, L76V, V82A, N88D) inhibitor, we applied multiple molecular dynamics (MMD) simulations along energy analysis by mechanics...
Cytochrome P450 (CYP) 3A7 plays a crucial role in the biotransformation of metabolized endogenous and exogenous steroids. To compare metabolic capabilities CYP3A7–ligands complexes, three ligands were selected, namely dehydroepiandrosterone (DHEA), estrone, estradiol. In this study, three-dimensional model CYP3A7 was constructed by homology modeling using crystal structure CYP3A4 as template refined molecular dynamics simulation (MD). The docking method adopted, combined with MD mechanics...