• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3429-3443
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• 2013

Chemokine receptor (CCR2) is a G protein-coupled receptor that contains seven transmembrane helices. Recent pharmaceutical research has focused on the antagonism of CCR2 and candidate drugs are currently undergoing clinical studies for the treatment of diseases like arthritis, multiple sclerosis, and type 2 diabetes. In this study, we analyzed the time dependent behavior of CCR2 docked with a potent 4-azetidinyl-1-aryl-cyclohexane (4AAC) derivative using molecular dynamics simulations (MDS) for 20 nanoseconds (ns). Homology modeling of CCR2 was performed and the 4AAC derivative was docked into this binding site. The docked model of selected conformations was then utilized to study the dynamic behavior of the 4AAC enzyme complexes inside lipid membrane. MDS of CCR2-16b of 4AAC complexes allowed us to refine the system since binding of an inhibitor to a receptor is a dynamic process and identify stable structures and better binding modes. Structure activity relationships (SAR) for 4AAC derivatives were investigated and reasons for the activities were determined. Probable binding pose for some CCR2 antagonists were determined from the perspectives of binding site. Initial modeling showed that Tyr49, Trp98, Ser101, Glu291, and additional residues are crucial for 4AAC binding, but MDS analysis showed that Ser101 may not be vital. 4AAC moved away from Ser101 and the hydrogen bonding between 4AAC and Ser101 vanished. The results of this study provide useful information regarding the structure-based drug design of CCR2 antagonists and additionally suggest key residues for further study by mutagenesis.

• The Korean Journal of Pharmacology
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• v.20 no.2
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• pp.23-34
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• 1984

To investigate diurnal variations of opiate receptor binding and its modification by experimental condition or treatment of various centrally-acting drugs, the amount of maximum $^3H-morphine$ binding in rat midbrain homogenates was measured at 4 hour intervals for 24 hours. Animals were conditioned under the controlled L : D, 12 : 12 cycle or D: D, 12 : 12 cycle, for 3 weeks and treated with 0.5 ml of physiological saline or drugs for 2 weeks. A highly significant diurnal rhythm with peak at 22 hour of early dark phase with an amplitude$(0.68{\pm}0.06\;pmole/mg\;protein)$ of +51.1% and nadir $(0.33{\pm}0.03\;mole/mg\;prtein)$ at 18 hour of late light phase with an amplitude of -26.6% was found in control group. 24 tour mean of $^3H-morphine$ binding was $0.45{\pm}0.03\;pmole/mg$ protein respectively. Constant dark adaptation or treatment of reserpine, pargyline, imipramine, amphetamine and chlorpromazine modified the diurnal rhythm in the time of peak and nadir binding shape, phase, amplitude of the diurnal curve and 24 hour mean of $^3H-morphine$ binding. However, Kd values were not changed in all experimental groups : Statistical analysis at times of least and great binding indicates that the differences in $^3H-morphine$ binding were due to changes not in the affinity, but in the number of binding sites. The results are interpreted with regard to the diurnal rhythm of opiate receptor finding. The modes of action of psychoactive drugs are closely related to postulated changes of receptor sensitivity in neuropharmacological aspects.

• Structural Engineering and Mechanics
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• v.8 no.5
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• pp.491-504
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• 1999

The initiation of toppling is explored for a uniform stack of blocks that rotates slowly about its mid-base. As the stack passes through its vertical position ($\theta$=0), it is in free-fall rotation, and a critical inclination angle ${\theta}_c$ is reached at which the toppling stack "fails" or begins to crack or separate. For tall stacks (high aspect ratios), two modes of failure are hypothesized, for which the dynamic failure analyses are shown to correlate with experimental results. These block failure modes are similar to those observed for tall, toppling masonry structures with weak binding material between their brick or stone blocks.

• Textile Coloration and Finishing
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• v.2 no.2
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• pp.33-38
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• 1990

Nitrocellulose [NC]-Poly(vinylamine) [PVAm] blended membranes with the change of amino group contents were prepared. The sorption and permeation of a mono-sulfonic acid dye, Orange II, in the membranes were investigated by the steady-state permeation method at $50^{\circ}C$ and pH 2.2. The results were discussed in the framework of dual sorption and diffusion theory. It was found that thesorption isotherms comprise a partition and two Langmuir type adsorption having similar binding constants. One of the latter sorption modes is due to unknown adsorption sites in NC and the other is due to the amino groups in PVAm. Apparent diffusion coefficients for collective P and L dye species, $D_P\; and D_L$, were obtained. Interpretation of $D_P$ values leads to two modes of partitions; one is such that dye is immobilized in NC and the other is the dissolution of the dye into the internal water phase.

• 한국정보디스플레이학회:학술대회논문집
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• 2003.07a
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• pp.1112-1117
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• 2003

Polarized Fourier transform infrared (IR) absorption is used to probe molecular conformation in a ferroelectric liquid crystal (FLC) during the reorientation induced by the external field. Spectra of planar aligned cells of FLC W314 are measured as functions of IR polarizer orientation and electric field applied to the FLC. The time evolution of the dichroism of the absorbance due to biphenyl core and alkyl tail molecular vibration modes, is observed. Static IR dichroism experiments show a W314 dichroism structure in which the principal axis of dielectric tensor from molecular core vibration are tilted further from the smectic layer normal than those of the tail. This structure indicates the effective binding site in which the molecules are confined in the Sm-C phase has, on average, "zig-zag" shape and this zig-zag binding site structure is rigidly maintained while the molecular axis rotates about the layer normal during field-induced switching.

• Journal of Industrial and Engineering Chemistry
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• v.67
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• pp.293-300
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• 2018

Lipocalins are diverse group of small extracellular proteins found in various organisms. In this study, members of 10 non-homologous lipocalin-ligand crystal complex structures were remodeled using rigid and flexible ligand modes to validate the prediction efficiency of molecular docking simulation. The modeled ligand conformations indicated a high prediction accuracy in rigid ligand mode using cluster based analysis for most cases whereas the flexible ligand mode required further considerations such as ligand binding energy and RMSD for some cases. This in silico study is expected to serve as a platform in the screening of novel ligands against lipocalin family of proteins.

• Bulletin of the Korean Chemical Society
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• v.27 no.9
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• pp.1445-1449
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• 2006

Molecular tweezers based on chenodeoxycholic acid bearing different lengths of arm were synthesized andtheir anion binding affinities were evaluated by $^1H$ NMR, isothermal calorimetric titration, and ESI mass spectrometry. Molecular tweezer 6 showed a high selectivity toward $H_2PO_4\;^-$ over $Cl^-,\;Br^-,\;I^-, $ and $CH_3CO_2\;^-$ by $^1H$ NMR titration, whereas the association constant for $F^-$ revealed the largest value as determined by ITC. The selectivity of 6 towards $F^-$ was about 103 times higher than that of $Cl^-,\;H_2PO_4\;^- $, and $CH_3CO_2\;^-$. ITCexperiment of 6 with $F^-$ in a DMSO showed two binding modes; two sequential association constants $K_1\;=\;2.77\;{\times}\;10^5\;M^{-1}$ and $K_2\;=\;8.68\;{\times}\;10^6\;M^{-1}$ were found. These sequential bindings were confirmed by ESI massspectrometry. 1 : 1 and 1 : 2 complexes of 6 and $F^-$ were found at m/z 868.08 and 884.04.

• Bulletin of the Korean Chemical Society
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• v.34 no.6
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• pp.1673-1678
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• 2013

Lumazine protein is a member of the riboflavin synthase superfamily and the intense fluorescence is caused by non-covalently bound to 6,7-dimethyl 8-ribityllumazine. To figure out the binding modes and the structure of the N-terminal domain of lumazine protein, the wild type of protein extending to amino acid 118 (N-LumP 118 Wt) and mutants of N-LumP 118 V41W, S48W, T50W, D64W, and A66W from Photobacterium leiognathi were purified. The biochemical properties of the wild type and mutants of N-LumP 118 proteins were analyzed by absorbance and fluorescence spectroscope. The peak of absorbance and fluorescence of lumazine ligand were shifted to longer wavelength on binding to N-LumPs. The observed absorbance value at 410 nm of lumazine bound to N-LumP 118 proteins indicate that one mole of N-LumP 118 proteins bind to one mole of ligand of lumazine. Fluorescence analysis show that the maximum peak of fluorescence of N-LumP S48W was shifted to the longest wavelength by binding with 6,7-dimethyl 8-ribityllumazine and was shown to the greatest quench effect by acrylamide among all tryptophan mutants.

• Bulletin of the Korean Chemical Society
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• v.31 no.5
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• pp.1314-1318
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• 2010

The $[Ru(tpy)_2]Cl_2$ (tpy:2,2':6',2"-terpyridine) complex was synthesized and its structure was confirmed by $^1H$-NMR and elemental analysis. Its binding mode toward DNA was compared with the well-known $[Ru(bpy)_3]Cl_2$ (bpy:2,2-bipyridyl), using isotropic absorption, linear dichroism(LD) spectroscopy, and an energy minimization study. Compared to $[Ru(bpy)_3]^{2+}$, the $[Ru(tpy)_2]^{2+}$ complex exhibited very little change in its absorption pattern, especially in the MLCT band, upon binding to DNA. Furthermore, upon DNA binding, both Ru(II) complexes induced a decrease in the LD magnitude in the DNA absorption region. The $[Ru(tpy)_2]^{2+}$ complex produced a strong positive LD signal in the ligand absorption region, which is in contrast with the $[Ru(bpy)_3]^{2+}$ complex. Observed spectral properties led to the conclusion that the interaction between the ligands and DNA bases is negligible for the $[Ru(tpy)_2]^{2+}$ complex, although it formed an adduct with DNA. This conclusion implies that both complexes bind to the surface of DNA, most likely to negatively charged phosphate groups via a simple electrostatic interaction, thereby orienting to exhibit the LD signal. The energy minimization calculation also supported this conclusion.

• Bulletin of the Korean Chemical Society
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• v.31 no.6
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• pp.1615-1620
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• 2010

Bis-[dipyrido[3,2-$\alpha$:2',3'-c]phenazine)$_2$(1,10-phenanthroline)$_2Ru_2$]$^{2+}$ complexes (bis-Ru(II) complexes) tethered by linkers of various lengths were synthesized and their binding properties to DNA investigated by normal absorption and linear dichroism spectra, and fluorescence techniques in this study. Upon binding to DNA, the bis-Ru(II) complex with the longest linker (1,3-bis-(4-pyridyl)-propane), exhibited a negative $LD^r$ signal whose intensity was as large as that in the DNA absorption region, followed by a complicate $LD^r$ signal in the metal-to-ligand charge transfer region. The luminescence intensity of this bis-Ru(II) complex was enhanced. The observed $LD^r$ and luminescence results resembled that of the [Ru(1,10-phenanthroline)$_2$ dipyrido[3,2-$\alpha$:2',3'-c]phenazine]$^{2+}$ complex, whose dipyrido[3,2-$\alpha$:2',3'-c]phenazine (dppz) ligand has been known to intercalate between DNA bases. Hence, it is conclusive that both dppz ligands of the bis-Ru(II) complex intercalate. The binding stoichiometry, however, was a single intercalated dppz per ~ 2.3 bases, which violates the "nearest binding site exclusion" model for intercalation. The length between the two Ru(II) complexes may be barely long enough to accommodate one DNA base between the two dppz ligands, but not for two DNA bases. When the linker was shorter (4,4'-bipyridine or 1,2-bis-(4-pyridyl)-ethane), the magnitude of the LD in the dppz absorption region, as well as the luminescence intensity of both bis-Ru(II) complexes, was half that of the bis-Ru(II) complex bearing a long linker. This observation can be elucidated by a model whereby one of the dppz ligands intercalates while the other is exposed to the aqueous environment.