• Archives of Pharmacal Research
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• v.10 no.1
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• pp.29-35
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• 1987

The effect of drug addition on the bovine serum albumin (BSA)-edible dye complex was studied by spectrophotometric method. The edible dyes tested were amranth, erythrosine, tatrazine and sunset yellow. The moles of bound dye per protein mole and free energies for edible dyes bounded were determined at pH 7.4. The values of free energy change by the addition of drughs to BSA-edible dye were ranged fro -6, 260 to 08030 cal/mole. In the wide range of edible dye concentration (0.3-$7{\times}10^{-5}$$^{-5}$ M), acetylsalicylic acid (ASA) showed pattern of displacement different from that of dye. It was assumed that ASA has different binding mechanisms from edible dye.

• Bulletin of the Korean Chemical Society
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• v.31 no.10
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• pp.2823-2829
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• 2010

We investigated the solvent effects on the relative free energies of binding of $Na^+$ and $Li^+$ ions to 12-crown-4 and ${\Delta}log\;K_s$ (the difference of stability constant of binding) by a Monte Carlo simulation of statistical perturbation theory (SPT) in several solvents. Comparing the relative free energies of binding of $Na^+$ and $Li^+$ ions to 12-crown-4, in $CH_3OH$ of this study with experimental works, there is a good agreement among the studies. We have reported the quantitative free energy polarity (of solvent) relationships (QFPR) of the relationship between the relative free energies and solvent polarity studied on the solvent effects on the relative free energies of binding of $Na^+$ and $Li^+$ ions to 12-crown-4.

• Journal of Integrative Natural Science
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• v.5 no.4
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• pp.216-219
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• 2012

Structure-based drug design possibly benefit from in silico methods that precisely predict the binding affinity of small molecules to target macromolecules. There are many limitations arise from the difficulty of predicting the binding affinity of a small molecule to a biological target with the current scoring functions. There is thus a strong interest in novel methodologies based on MD simulations that claim predictions of greater accuracy than current scoring functions, helpful for a regular use designed for drug discovery in the pharmaceutical industry. Herein, we report a short review on free energy calculations using MMPBSA method a useful method in structure based drug discovery.

• Bulletin of the Korean Chemical Society
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• v.26 no.9
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• pp.1421-1426
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• 2005

The stationary point structures and relative energies between them as well as binding energies of $(CO)_2$ have been investigated at the CCSD(T) level using the correlation-consistent basis sets aug-cc-pVXZ(X=T,Q,5). It is found that while the equilibrium structure corresponds to the C-bonded T-shaped configuration with intermolecular distance of 4.4 $\AA$, there exists another minimum, slightly higher in energy ($\sim$10 $cm^{-1}$) than the global minimum, corresponding to the O-bonded T-shaped configuration with the intermolecular distance of 3.9 $\AA$. The CCSD(T) basis set limit binding energy of $(CO)_2$ is estimated to be 132 $cm^{-1}$.

• Bulletin of the Korean Chemical Society
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• v.32 no.spc8
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• pp.3051-3056
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• 2011

We calculate the free energy surfaces for two small proteins and a protein-RNA complex system by using a lattice model approach. In particular, we employ the Munoz-Eaton model, which is a native-structure based statistical mechanical model for studying protein folding problem. The model can provide very useful insights into the folding mechanisms by allowing one to calculate the free energy surfaces efficiently. We first calculate the free energy surfaces of ubiquitin and BBL, using both approximate and recently developed exact solutions of the model. Ubiquitin exhibits a typical two-state folding behavior, while BBL downhill folding in our study. We then extend the method to study of a protein-RNA complex. In particular, we focus on PAZ-siRNA complex. In order to elucidate the interplay between folding and binding kinetics for this system we perform comparative studies of PAZ only, PAZ-siRNA complex and two mutated complexes. We find that folding and binding are strongly coupled with each other and the bound PAZ is more stable than the unbound PAZ. Our results also suggest that the binding sites of the siRNA may serve act as a nucleus in the folding process.

• Proceeding of EDISON Challenge
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• 2014.03a
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• pp.63-74
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• 2014

Predicting protein loop structures is an important modeling problem since protein loops are often involved in diverse biological functions by participating in enzyme active sites, ligand binding sites, etc. However, loop structure prediction is difficult even when structures of homologous proteins are known due to large sequence and structure variability among loops of homologous proteins. Therefore, an ab initio approach is necessary to solve loop modeling problems. One of the difficulties in the development of ab initio loop modeling method is to derive an accurate scoring function that closely approximates the true free energy function. In particular, entropy as well as energy contribution have to be considered adequately for loops because loops tend to be flexible compared to other parts of protein. In this study, the contribution of conformational entropy is considered in scoring loop conformations by employing "colony energy" which was previously proposed to estimate the free energy for an ensemble of conformations. Loop conformations were generated by using two EDISON_Chem programs GalaxyFill and GalaxySC, and colony energy was designed for this sampling by tuning relevant parameters. On a test set of 40 loops, the accuracy of predicted loop structure improved on average by scoring with the colony energy compared to scoring by energy alone. In addition, high correlation between colony energy and deviation from the native structure suggested that more extensive sampling can further improve the prediction accuracy. In another test on 6 ligand-binding loops that show conformational changes by ligand binding, both ligand-free and ligand-bound states could be identified by using colony energy when no information on the ligand-bound conformation is used.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.269-274
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• 1996

The binding interactions between human serum albumin (HSA) and the edible food dyes amaranth, tartrazine and sunset yellow have been studied. Intrinsic association constants and the free energy changes associated with dye-protein binding at physiological pH for amaranth and tartrazine, and at two different pH values for sunset yellow have been calculated from ultrafiltration data. The temperature dependence $(20-40^{\circ}C)$ of the intrinsic association constants at pH 7.4 for amaranth-HSA and tartrazine-HSA mixtures have been measured, from which a plot of the van't Hoff isochore exhibits a marked change in slope around $30^{\circ}C$ indicating a possible change in protein conformation. The number of dye binding sites on HSA is reported for all the above conditions. HSA-ligand binding enthalpies have been used in conjunction with the N-B transitional binding enthalpy for HSA, to calculate the enthalpy for the N-B transition when ligands are bound with the protein.

• BMB Reports
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• v.29 no.1
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• pp.1-10
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• 1996

The binding interaction of ethidium to a series of synthetic deoxyoligonucleotides containing a B-Z junction between left-handed Z-DNA and right-handed B-DNA, was studied. The series of deoxyoligonucleotides was designed so as to vary a dinucleotide step immediately adjacent to a B-Z junction region. Ethidium binds to the right-handed DNA forms and hybrid B-Z forms which contain a B-Z junction, in a highly cooperative manner. In a series of deoxyoligonucleotides, the binding affinity of ethidium with DNA forms which were initially hybrid B-Z forms shows over an order of magnitude higher than that with any other DNA forms, which were entirely in B-form DNA The cooperativity of binding isotherms were described by an allosteric binding model and by a neighbor exclusion model. The binding data were statistically compared for two models. The conformation of allosterically converted DNA forms under binding with ethidium is found to be different from that of the initial B-form DNA as examined by CD spectra. The ratio of the binding constant was interestingly correlated to the free energy of base unstacking and the conformational conversion of the dinucleotide. The more the base stacking of the dinucleotide is unstable, or the harder the conversion of B to A conformation, the higher the ratio of the binding constant of ethidium with the allosterically converted DNA forms and with the initial B-Z hybrid forms. DNA sequence around a B-Z junction region affects the binding affinity of ethidium. The results in this study demonstrate that ethidium could preferentially interact with unusual DNA structures.

• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.162-168
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• 2011

Many ligands have been experimentally designed and tested for their activities as inhibitors against bacterial enoyl-ACP reductase (FabI), ENR. Here the binding energies of the reported ligands with the E. coli ENR-$NAD^+$ were calculated, analyzed and compared, and their molecular dynamics (MD) simulation study was performed. IDN, ZAM and AYM ligands were calculated to have larger binding energies than TCL and IDN has the largest binding energy among the considered ligands (TCL, S54, E26, ZAM, AYM and IDN). The contribution of residues to the ligand binding energy is larger in E. coli ENR-NAD+-IDN than in E. coli ENR-$NAD^+$-TCL, while the contribution of $NAD^+$ is smaller for IDN than for TCL. The large-size ligands having considerable interactions with residues and $NAD^+$ have many effective functional groups such as aromatic $\pi$ rings, acidic hydroxyl groups, and polarizable amide carbonyl groups in common. The cation-$\pi$ interactions have large binding energies, positively charged residues strongly interact with polarisable amide carbonyl group, and the acidic phenoxyl group has strong H-bond interactions. The residues which have strong interactions with the ligands in common are Y146, Y156, M159 and K163. This study of the reported inhibitor candidates is expected to assist the design of feasible ENR inhibitors.

• Proceeding of EDISON Challenge
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• 2016.03a
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• pp.62-66
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• 2016

Tumor suppressor protein p53 loses its function upon binding with the HDM2 protein, and inhibiting the p53-HDM2 interaction is critical to suppress tumor cell growth. Recently, the cyclized helix-loop-helix peptide (cHLH) mimicking the ${\alpha}-helix$ part of the p53 protein has been designed and found to exhibit high binding affinity with HDM2. Here, we report the structural and thermodynamic characteristics of the bound complex of the cHLH peptide with the HDM2 protein. We performed molecular dynamics simulations to investigate the structural features of the cHLH peptide as well as its complex with the HDM2. The binding free energy calculation based on the integral equation theory was also executed to quantify the binding affinity for the cHLH/HDM2 complex and to understand the factors contributing to the binding affinity. We found a variety of factors for the helix stability of the cHLH peptide as well as in the complexation with the HDM2, which may provide an insight into the development of anti-cancer drug designs.