• Bulletin of the Korean Chemical Society
• /
• 제20권3호
• /
• pp.345-351
• /
• 1999

The structures, the energetics, and the spectra of K+(H2O)3 have been studied at HF and MP2 levels with the basis set of triple-zeta plus two sets of polarization functions (TZ2P) for water molecules. Two structures considered are 3+0 (D3), and 2+1 (C2v). The 2+1 (C2v) has two hydrogen bonds between the primary hydration and the secondary hydration shell water molecules. They have similar binding energy and enthalpy. The most stable conformation of K+(H2O)3 is entropy driven as shown in Na+(H2O)5 and in Na+(H2O)6 cases. The 3+0 (D3) conformation is the most stable at 298 K and at 1 atm, based on Gibbs free energy changes (ΔGr). The thermal contributions to the enthalpy and the Gibbs free energy are corrected for the low frequency modes. The corrected ΔGr is in good agreement with the experimental value. Vibrational frequencies of two conformations are revealed as their characteristics.

• Bulletin of the Korean Chemical Society
• /
• 제33권3호
• /
• pp.770-774
• /
• 2012

Protein loops are often involved in diverse biological functions, and some functional loops show conformational changes upon ligand binding. Since this conformational change is directly related to ligand binding pose and protein function, there have been numerous attempts to predict this change accurately. In this study, we show that it is plausible to obtain meaningful ensembles of loop conformations for flexible, ligand-binding protein loops efficiently by applying a loop modeling method. The loop modeling method employs triaxial loop closure algorithm for trial conformation generation and conformational space annealing for global energy optimization. When loop modeling was performed on the framework of ligand-free structure, loop structures within $3\AA$ RMSD from the crystal loop structure for the ligand-bound state were sampled in 4 out of 6 cases. This result is encouraging considering that no information on the ligand-bound state was used during the loop modeling process. We therefore expect that the present loop modeling method will be useful for future developments of flexible protein-ligand docking methods.

• 한국자기공명학회논문지
• /
• 제19권2호
• /
• pp.67-73
• /
• 2015

The microcystin is a cyclic heptapeptide from metabolites of cyanobacteria in the genera mycrocystis, anabaeba as a result of eutrophication. It has been known that microcystin-LR is a potent inhibitor of the catalytic subunits of protein phosphatase-1 (PP-1) as well as powerful tumor promoter. The active site of microcystin actually has two metal ions $Fe^{2+}/Zn^{2+}$ close to the nucleophilic portion of PP-1-microcystin complex. We report the isolation and purification of this microcystin-LR from cyanobacteria (blue-green algae) obtained from Daechung Dam in Chung-cheong Do, Korea. Microcystin-LR was extracted from solid-phase extraction (SPE) sample preparation using a CN cartridge. The cyanobacteria extract was purified to obtain microcystin-LR by HPLC method and identified by LC/MS. The detail structural studies that can elucidate the possible role of monovalent and divalent metal ions in PP-1-microcystin complexation were carried out by utilizing molecular dynamics. Conformational changes in metal binding for ligands were monitored by molecular dynamic computation and potential of mean force (PMF) using the method of the free energy perturbation. The microcystin-metal binding PMF simulation results exhibit that microcystin can have very stable binding free energy of -10.95 kcal/mol by adopting the $Mg^{2+}$ ion at broad geometrical distribution of $0.5{\sim}4.5{\AA}$, and show that the $K^+$ ion can form a stable metal complex rather than other monovalent alkali metal ions.

• 대한핵의학회지
• /
• 제16권1호
• /
• pp.23-30
• /
• 1982

Serum thyroxine binding globulin (TBG) was measured with a radioimmunoassay (RIA) kit (GammaDab TBG). The TBG concentration in 23 adult normals was $23.7{\pm}1.9{\mu}g/ml(mean{\pm}SD)$. The serum TBG levels of $21.6{\pm}3.5{\mu}g/ml$) in hyperthyroidism, $24.7{\pm}4.9{\mu}g/ml$ in subacute thyroiditis, $20.7{\pm}7.0{\mu}g/ml$ in liver cirrhosis and $22.6{\pm}3.7{\mu}g/ml$ in sick patient were not significantly different from normals. The levels of $31.8{\pm}5.9{\mu}g/ml$ in hypothyroidism, $36.2{\pm}5.1{\mu}g/ml$ in pregnancy (p<0.01, p<0.001) and $29.3{\pm}6.1{\mu}g/ml$ in molar pregnancy (p<0.01) were significanty higher that in normals. In various cases without thyroid dieases (euthroid group), the TBG concentration correlated with the value for Amerlex $T_3$ (r=0.816) though there was curvilinear relationship. This relationship was altered in hyperthyroidism, subacute thyroiditis and molar pregnancy in which sera were overloaded with thyroxine $(T_4)$ so that concentration of unoccupied binding sites on TBG (free TBG concentration) were more decreased than expected from normal TBG concentrations. Hypothyroidism was also separated from the curvilinear relationship in euthyroid group indicating that free TBG concentrations were more increased relative to slightly increased TBG concentrations. Measurement of the TBG concentration was considered useful in the diagnosis of TBG defiency, in differentiating molar pregnancy from hyperthyroidism and for correct understanding the hormone binding in liver dieases and other nonthyroidal illness.

• Bulletin of the Korean Chemical Society
• /
• 제33권8호
• /
• pp.2669-2674
• /
• 2012

Crown ether is one of well-known host molecules and able to selectively sequester metal cation. We employed M06-2X density functional theory with IEFPCM and SMD continuum solvation models to study selectivity of dibenzo-18-crown-6-ether (DB18C6) for alkaline earth dications, $Ba^{2+}$, $Sr^{2+}$, $Ca^{2+}$, and $Mg^{2+}$ in the gas phase and in aqueous solution. $Mg^{2+}$ showed predominantly strong binding affinity in the gas phase because of strong polarization of CO bonds by cation. In aqueous solution, binding free energy differences became smaller among these dications. However, $Mg^{2+}$ had the best binding, being incompatible with experimental observations in aqueous solution. The enthalpies of the dication exchange reaction between DB18C6 and water cluster molecules were computed as another estimation of selectivity in aqueous solution. These results also demonstrated that $Mg^{2+}$ bound to DB18C6 better than $Ba^{2+}$. We speculated that the species determining selectivity in water could be 2:1 complexes of two DB18C6s and one dication.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권8호
• /
• pp.3601-3606
• /
• 2014

Single nucleotide polymorphisms located at microRNA (miRNA)-binding sites are likely to affect the expression of miRNA targets and may contribute to the susceptibility of humans to common diseases. Here 335 candidate lung cancer-related inflammatory genes were selected according to the existing literature and database. We identified putative miRNA-binding sites of 149 genes by specialised algorithms and screened SNPs in the 3'UTRs of these genes. By calculating binding free energy, we sorted 269 SNPs on the basis of the possibility of prediction. The proposed approach could help to easy the identification of functionally relevant SNPs and minimize the workflow and the costs.

• 한국자기공명학회논문지
• /
• 제10권2호
• /
• pp.163-174
• /
• 2006

Luteinizing Hormone Releasing Hormone(LHRH) is a decapeptide neurotransmitter known to be regulated by metal ions in the hyperthalamus. Zn-binding LHRH complex was systhesized, and zinc-LHRH complex was studied to understand what kinds of structural modifications would be critical in the LHRH releasing mechanism. Both nonexchangeable and exchangeable $^1H-NMR$ signal assignments were accomplished by pH-dependent and COSY NMR experiments. In addition, $^1H-NMR$ chemical shift changes of a-proton and peptide NH NMR signals at different pH condition, and $^1H-NMR$ signal differences between metal free and metallo-LHRH complex was monitored. NMR signals exhibit that primary metal-binding sites are nitrogens donor of imidazole ring and Arg, and peptide oxygen of Pro-His in the sequence. Structure obtained in this study has a cyclic conformation which is similar to that of energy minimized, and exhibits a specific a-helical turn with residue numbers $(2{\sim}7)$ out of 10 amino acids.

• 통합자연과학논문집
• /
• 제9권3호
• /
• pp.166-170
• /
• 2016

Collagen plays a vital role in the maintenance of structure and function of a human body. It has been widely applied in various fields including biomedical, cosmeceutical, food, pharmaceutical and tissue engineering. In the present study, the docking behaviour of type I collagen with 15 different ligands namely hydroxymethylfurfural, methylglyoxal, methylsyringate, O-methoxyacetophenone, 3-phenyllactic acid, 4-hydroxybenzoic acid, kojic acid, lumichrome, galangin, artoindonesianin F, caffeic acid, 4-coumaric acid, origanol A, thymoquinone and quercetin was evaluated along with their putative binding sites using Discovery Studio Version 3.1. Docking studies and binding free energy calculations revealed that origanol A has maximum interaction energy (-40.48 kcal/mol) and quercetin with the least interaction energy (-15.44 kcal/mol) as compared to the other investigated ligands. Three ligands which are galangin, methylsyringate and origanol A were shown to interact with Asp21 amino acid residue of chain B (type I collagen). Therefore, it is strongly suggested that the outcomes from the present study might provide new insight in understanding these 15 ligands as potential type I collagen modulators for the prevention of collagen associate disorders.

• 통합자연과학논문집
• /
• 제10권1호
• /
• pp.1-6
• /
• 2017

Demand for a new anti-malarial drug has been dramatically increasing in the recent years. Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR) plays a vital role in fatty acid elongation process, which now emerged as a new important target for the development of anti-microbial and anti-parasitic molecules. In the present study, 19 compounds namely alginic acid, atropine, chlorogenic acid, chrotacumine A & B, coenzyme $Q_1$, 4-coumaric acid, curcumin, ellagic acid, embelin, 5-O-methyl embelin, eugenyl glucoside, glabridin, hyoscyamine, nordihydroguaiaretic acid, rohitukine, scopolamine, tlatlancuayin and ursolic acid were evaluated on their docking behaviour on P. falciparum enoyl-acyl carrier protein reductase (PfENR) using Auto dock 4.2. The docking studies and binding free energy calculations exhibited that glabridin gave the highest binding energy (-8.07 kcal/mol) and 4-coumaric acid in contrast showed the least binding energy (-4.83 kcal/mol). All ligands except alginic acid, ellagic acid, hyoscyamine and glabridin interacted with Gln409 amino acid residue. Interestingly four ligands namely coenzyme $Q_1$, 4-coumaric acid, embelin and 5-O-methyl embelin interacted with Gln409 amino acid residue present in both chains (A & B) of PfENR protein. Thus, the results of this present study exhibited the potential of these 19 ligands as P. falciparum enoyl-acyl carrier protein reductase (PfENR) inhibitory agents and also as anti-malarial agents.

• Bulletin of the Korean Chemical Society
• /
• 제22권11호
• /
• pp.1248-1254
• /
• 2001

The conformations and energies of p-tert-butylcalix[4]crown-6-ether (1) and its alkyl ammonium complexes have been calculated by ab initio HF/6-31G quantum mechanics method. The cone conformation was found to be most stable for free host 1. We hav e determined the binding site of these host-guest complexes focusing on the crown-6-ether or p-tert-butylcalix[4]arene pocket of the cone conformation of host molecule 1. The primary binding site of host 1 for the recognition of alkyl ammonium guests was confirmed to be the central part of the crown moiety of cone conformation. The complexation energy calculations revealed that the ammonium cation without alkyl group showed the highest complexation efficiency when combined with host 1, that is in satisfactory agreement with the experimental results.