A5061258590- Crystallization and Solubility Studies
- Porphyrin and Phthalocyanine Chemistry
- X-ray Diffraction in Crystallography
- Protein Structure and Dynamics
- HIV/AIDS drug development and treatment
- Enzyme Structure and Function
- Lipid Membrane Structure and Behavior
- Porphyrin Metabolism and Disorders
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Hemoglobin structure and function
- Metal-Catalyzed Oxygenation Mechanisms
- Antibiotic Resistance in Bacteria
- Protein purification and stability
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Molecular Junctions and Nanostructures
- RNA and protein synthesis mechanisms
- Mass Spectrometry Techniques and Applications
- Semiconductor materials and devices
- Crystallography and molecular interactions
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Pharmacogenetics and Drug Metabolism
- Antibiotics Pharmacokinetics and Efficacy
Chiba University
2015-2024
East China University of Science and Technology
2009-2010
Matsuyama University
2009
National Institute of Infectious Diseases
2007-2009
Chinese Academy of Sciences
2009
Shanghai Institute of Materia Medica
2009
Kitasato University
2009
Japan Science and Technology Agency
2005-2008
Tokyo Institute of Technology
1993-2008
Hosei University
2006
Abstract In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei Province, China. No specific treatment has been established against disease-2019 (COVID-19) so far. Therefore, it is urgently needed to identify effective antiviral agents for the of this disease, and several approved drugs such as lopinavir have evaluated. Here, we report that nelfinavir, an HIV-1 protease inhibitor, potently inhibits replication SARS-CoV-2. The concentrations 50%...
Accumulation and fibril formation of amyloid β (Aβ) peptides onto a ganglioside-rich lipid membrane is cause neuro-disturbance diseases. To find out measure for suppressing the nucleation seed fibrils, mechanism initial binding Aβ to should be clarified. Molecular dynamics simulations were carried investigate adhesion process GM1-ganglioside-containing membrane. Multiple computational trials executed analyze probability occurrence by using calculation models containing mixed membrane, water...
Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the proteins that currently available anti-HIV-1 drugs target. Inhibitors HIV-1 PR have become available, and they lowered rate mortality from acquired immune deficiency syndrome (AIDS) in advanced countries. However, emergence drug-resistant variants quite high because their short retroviral life cycle mutation rate. Serious mutations against inhibitors (PIs) frequently appear at active site PR. Exceptionally, some other such...
The kinetic analysis of coumarin oxidation by CYP2A6 suggested that substrate binding and release occurred in the multiple steps such events proceeded rapidly. However, crystal structure CYP2A6-coumarin complex reveals no obvious channel is open enough to allow pass through. Thus, an intriguing important question arises: how enters exits active site, which deeply buried at center fold. In this study, geometric potential openings was first performed on all available structures CYP2A6. And...
GM1 gangliosides form a microdomain with sphingomyeline (SM) and cholesterol (Chol) are deeply involved in the aggregation of amyloid beta (Aβ) peptides on neural membranes. We performed molecular dynamics simulations two kinds lipid bilayers containing ganglioside: GM1/SM/Chol GM1/POPC. Both 10 100 ns another set different initial arrangement essentially showed same computational results. molecules membrane were condensed, whereas those GM1/POPC scattered. That is, formation cluster was...
The ability to predict patients' responses chemoradiotherapy by analyzing pre-treatment biopsy specimens would be valuable for managing oesophageal squamous-cell cancer. To this end, the expression of p53, thymidine phosphorylase and vascular endothelial cell growth factor was analyzed immunohistochemistry in 52 patients with cancer prior chemoradiotherapy. Treatment consisted radiotherapy (40 Gy) 5 day-infusion 5-Fluorouracil (500 mg m−2 per day) combined cisplatin (10 day). Following...
Nelfinavir (NFV) is a currently available HIV-1 protease (PR) inhibitor. Patients in whom NFV treatment has failed predominantly carry D30N mutants of PRs if they have been infected with the subtype B virus. In contrast, N88S emerge patients and who CRF01_AE Both confer resistance against NFV. However, it remains unclear why nonactive site mutation confers this study, we examined mechanism through computational simulations. The simulations suggested that despite mutation, causes by reducing...
A pair of myoglobins containing inherently distorted alpha-ethyl-2,4-dimethyldeuteroheme or undistorted 2,4-dimethyldeuteroheme were prepared, and the functional consequence intrinsic heme deformation was investigated. The visible absorption peaks myoglobin bearing exhibited a bathochromic shift, indicating that deformed in protein pocket. Ligand affinities for ferric with found to be higher than those heme. observation suggested iron atom more displaced toward proximal histidine weaken...
Cytochrome P450 (CYP) is deeply involved in the metabolism of chemicals including pharmaceuticals. Therefore, polymorphisms this enzyme have been widely studied to avoid unfavorable side effects drugs chemotherapy. In work, we performed computational analysis mechanism decrease enzymatic activity for three typical CYP 2C9 species: *2, *3, and *5. Based on equilibrated structure obtained by molecular dynamics simulation, volume binding pocket fluctuation amino residues responsible substrate...
Anti-HIV peptides with inhibitory activity against HIV-1 integrase (IN) have been found in overlapping peptide libraries derived from gene products. In a strand transfer assay using IN, active certain sequential motifs related to Vpr- and Env-derived were found. The addition of an octa-arginyl group the caused remarkable inhibition 3′-end-processing reactions catalyzed by IN significant HIV replication.
β2 Adrenergic receptor (β2AR) is a kind of G-protein coupled receptors (GPCRs) which transduce wide range extracellular signals into intracellular messages responsible for the regulation diverse cell functions. Because their functional ubiquity, GPCR one most important drug targets in pharmaceutical industry. Although recent crystallographic studies provided both active and inactive states some families GPCRs, influence lipid composition bilayer membrane on activation still poorly...
Influenza viruses are global threat to humans, and the development of new antiviral agents still demanded prepare for pandemics overcome emerging resistance current drugs. polymerase acidic protein N-terminal domain (PAN) has endonuclease activity is one appropriate targets novel agents. First, we performed X-ray cocrystal analysis on complex structures PAN with two inhibitors. The crystallization inhibitor soaking were done at pH 5.8. binding modes inhibitors different from a common mode...
Antibodies are one of the most important protein molecules in biopharmaceutics. Due to recent advance technology for producing monoclonal antibodies, many structural data available on antigen–antibody complexes. To characterize molecular interaction recognition, we computationally analyzed 500 complex structures by mechanics calculations. The presence Ser and Tyr is markedly large complementarity-determining regions (CDRs). Although abundant CDRs, its contribution binding score not large....
The substrate oxygenation mechanism by an ultimate species in monooxygenation cytochrome P-450 (compound I) was investigated the density functional theory method. An initial model compound constructed from a structure obtained 300-ps molecular dynamics simulation of I-formed P-450cam under physiologic conditions, and it consisted porphine for protoporphyrin IX, S-−CH3 side chain Cys357 fifth ligand heme, methane molecule substrate, heme iron, oxygen atom sixth heme. results calculation...
Abstract To raise the accuracy of force field for nucleic acids, several parameters were elaborated, focusing on rotation around χ torsion axis. The reliability molecular dynamics (MD) simulation was significantly increased by improving at C8N9C1′X (X = H1′, C2′, O4′) in A, G and those C6N1C1′X C, T, U. In this work, we constructed small models representing chemical structure G, U, estimated energy profile χ‐axis executing numerous quantum mechanical (QM) calculations. derived discrete...
The RNase H activity associated with human immunodeficiency virus type 1 (HIV-1) is an attractive target for antiretroviral drug development. We screened 20000 small-molecular-weight compounds inhibitors and identified a novel H-inhibiting structure characterized by 5-nitro-furan-2-carboxylic acid carbamoylmethyl ester (NACME) moiety. Two NACME derivatives, adamantan-1-carbamoylmethyl (compound 1) [[4-(4-bromo-phenyl)-thiazol-2-yl]-(tetrahydro-furan-2-ylmethyl)-carbamoyl]-methyl 2),...
Highly pathogenic influenza viruses have become a global threat to humans. It is important select an effective therapeutic option suitable for the subtypes in epidemic or pandemic. To increase options, development of novel antiviral agents acting on targets different from those currently approved drugs required. In this study, we performed molecular dynamics simulations spike protein viral envelop, hemagglutinin, wild-type and three kinds mutants using model system consisting trimeric...
Anti-PUF60, poly(U)-binding-splicing factor, autoantibodies are reported to be detected in the sera of dermatomyositis and Sjogren's syndrome that occasionally associated with malignancies. PUF60 is identical far-upstream element-binding protein-interacting repressor (FIR) a transcriptional c-myc gene. In colorectal cancers, splicing variant FIR lacks exon2 (FIRΔexon2) overexpressed as dominant negative form FIR. this study, reveal presence significance anti-FIRs (FIR/FIRΔexon2) antibodies...
Neuroblastoma (NB) is one of the most frequent solid tumors in children and its prognosis still poor. The neurotrophin receptor TrkB ligand brain-derived neurotrophic factor (BDNF) are expressed at high levels high-risk NBs involved defining poor patients. However, targeting therapy has never been realized clinic. We performed an silico screening procedure utilizing AutoDock/grid computing technology order to identify novel small chemical compounds BDNF-binding domain TrkB. For first...